CN1317031C - Efficient mixture preparation for intensifying solid tumor cell chemical therapeutic sensitivity - Google Patents
Efficient mixture preparation for intensifying solid tumor cell chemical therapeutic sensitivity Download PDFInfo
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- CN1317031C CN1317031C CNB2005100296232A CN200510029623A CN1317031C CN 1317031 C CN1317031 C CN 1317031C CN B2005100296232 A CNB2005100296232 A CN B2005100296232A CN 200510029623 A CN200510029623 A CN 200510029623A CN 1317031 C CN1317031 C CN 1317031C
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 12
- 239000002246 antineoplastic agent Substances 0.000 abstract 3
- 229940044683 chemotherapy drug Drugs 0.000 abstract 3
- 102000005157 Somatostatin Human genes 0.000 abstract 2
- 108010056088 Somatostatin Proteins 0.000 abstract 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 abstract 2
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- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 abstract 2
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Abstract
The present invention relates to a high-efficiency mixed preparation capable of enhancing chemotherapeutic susceptibility of solid tumor cells, which is prepared by mixing a drug influencing the regulation and the control of the period of the solid tumor cells and a period specificity chemotherapeutic drug according to certain concentration proportion, wherein the drug influencing the regulation and the control of the period of the solid tumor cells is somatostatin, and the period specificity chemotherapeutic drug is Gemzar. Compared with the single use of the chemotherapeutic drug, the killing effect is obviously improved after the mixed preparation of the somatostatin and the Gemzar is used.
Description
Technical field
The present invention relates to biomedical sector, relate in particular to a kind of efficient mixture preparation that can strengthen the solid tumor cell chemosensitivity.
Background technology
Entity tumor comprises the multiple malignant tumor of a plurality of systems of health such as mastocarcinoma, gastric cancer, carcinoma of gallbladder, carcinoma of prostate, is one of three serious diseases of harm people ' s health, initiation patient death.Though excision still is the first-selection of treatment means, for the patient behind the radical surgery, chemotherapy is the important means that cooperates operative treatment timely and effectively.For the patients with terminal of forfeiture surgical engine meeting, chemotherapy prolongs patient's key point of life cycle especially.Existing chemotherapy, bring into play exactly medicine cell cycle not simultaneously the blocking effect of phase kill and wound cancerous cell.Same chemotherapeutics shows different prognosis in the bullate treatment of different carcinoma, point out different tumors to there are differences aspect chemosensitivity, but its mechanism it be not immediately clear.Simultaneously, chemotherapeutics non-selectivity ground is to cytotoxic effect that human normal tissue produces, and promptly chemotherapy side effect has limited to improve the way that chemotherapeutics concentration improves its curative effect.Therefore, though clinically by combination, the route of administration that changes chemotherapeutics of setting up different chemotherapeutics, the methods such as new chemotherapeutics of researching and developing high-efficiency low-toxicity, the result is still not satisfied, entity tumor for the chemosensitivity extreme difference, as carcinoma of gallbladder, do not find effective Therapeutic Method at present clinically so far as yet.
Therefore, be the key link that influences patient's life span and life quality whether to the sensitivity of chemotherapy with the occurrence degree of chemotherapy side effect.Seeking effective drug regimen to improve the chemosensitivity of solid tumor cell, reduce the chemotherapeutics consumption and take place to reduce side reaction, is the important means that improves solid tumor patient survival rate and life quality, also is our purpose of the present invention.
Summary of the invention
The object of the present invention is to provide a kind of efficient mixture preparation that can strengthen the solid tumor cell chemosensitivity.
The objective of the invention is to realize by following technical method: the efficient mixture preparation that can strengthen the solid tumor cell chemosensitivity is that a kind of medicine and a kind of period specific chemotherapeutics that influences the solid tumor cell cycle regulating got according to certain concentration ratio is mixed.The medicine that wherein influences the solid tumor cell cycle regulating is Shi Taning (being called for short S), and the period specific chemotherapeutics is strong selecting (being called for short GZ, Z).
Found through experiments, after the use chemotherapeutics is executed the strong mix preparation of selecting of his peace, improve with chemotherapeutics the fragmentation effect of cancerous cell is obviously single.
Strengthen the application of mix preparation in preparation treatment solid tumor cell medicine of solid tumor cell chemosensitivity.Solid tumor cell is the carcinoma of gallbladder cell.
Description of drawings
Fig. 1 is the experimental result of drug influence cell growth cycle.
Fig. 2 is good for for Shi Taning is collaborative and selects performance to the inhibiting experimental result of tumor cell viability.
Fig. 3 is the collaborative strong experimental result that increases cell death inducing of selecting of Shi Taning.
Fig. 4 increases strong experimental result of selecting mass action in the cell for Shi Taning.
The specific embodiment
The efficient mixture preparation that the present invention strengthens the solid tumor cell chemosensitivity is that a kind of medicine and a kind of period specific chemotherapeutics that influences the solid tumor cell cycle regulating got according to certain concentration ratio is mixed.That adopt in the experiment of the present invention is Shi Taning, and the period specific chemotherapeutics is selected strong selecting for use.In the clinical practice, the concentration range of two kinds of compositions is that strong selecting is not higher than 3.5mg/ml, and Shi Taning is not higher than 150 μ g/ml.Being good for the preferred concentration of selecting with Shi Taning is: be good for and select 0.5～2.5mg/ml, execute his peaceful 62.5～150 μ g/ml.
Carcinoma of gallbladder cell GBC-SD purchases the cell bank in Shanghai Inst. of Cytobiology, Chinese Academy of Sciences among the present invention.Cell is incubated at 37 ℃, 5%CO with the RPMI1640 culture medium that contains 15% calf serum
2The constant temperature and humidity incubator.
Below in conjunction with embodiment the present invention is further described.
The active mensuration of embodiment 1MTT method pair cell
With the GBC-SD cell of exponential phase with 5 * 10
4The concentration of cell/ml is inoculated in 96 well culture plates, every hole 0.1ml.Matched group adds the not culture medium of pastille, the strong group of selecting adds respectively and contains the strong culture medium of selecting of variable concentrations and handle, the drug combination group adds respectively and contains strong the selecting with the culture medium of 62.5 μ g/ml Shi Taning of variable concentrations (0.5mg/ml, 1.0mg/ml, 1.5mg/ml, 2.0mg/ml, 2.5mg/ml, 3.0mg/ml, 3.5mg/ml) and handle every group of parallel 5 holes of concentration.Place 37 ℃, 5%CO
2The constant temperature and humidity incubator was cultivated 3 days, experiment stops preceding 4 hours every holes and adds 5mg/mlMTT 10 μ l, cultivate and finish the every hole adding in back 0.04N DMSO (dimethyl sulfoxide), every hole 100 μ l, vibration 10min dissolves the MTT reduzate fully, with BioRad 550 type microplate reader, with 550nm is the experiment wavelength, and 655nm is for to measure its trap with reference to wavelength.Map with the variable concentrations of medicine and the survival rate of cell.Can measure the medicine of variable concentrations and medication combined effect influence by this method accurately and effectively to the carcinoma of gallbladder cytoactive.As can be seen from Figure 1, the medication group is in the cell number of S phase and will illustrates that the growth cycle of medicine pair cell has certain influence apparently higher than negative control group.As can be seen from Figure 2, strong selecting under higher concentration has certain inhibitory action to the carcinoma of gallbladder cell activity, but when with the Shi Taning synergy of 62.5 μ g/ml after, this inhibitory action is obviously strengthened.Under the synergism of Shi Taning, 0.2mg/ml strong selects that effect of carcinoma of gallbladder cell inhibiting and 3.2mg/ml strong selected the effect of independent effect is suitable.And the inhibition effect of drug combination group will be significantly better than the effect of the independent effect of two kinds of medicines.This shows that executing him would rather be with the collaborative strong inhibitory action of performance to tumor cell viability of selecting.
Embodiment 2 flow cytometries (FCAS)
With the GBC-SD cell of exponential phase with 10
5Cellml
-1Concentration be inoculated in the 3.5cm culture dish, every ware 5ml, matched group add the not culture medium of pastille, are good for to select to organize to add to contain the strong culture medium processing of selecting of 1mg/ml, the adding of drug combination group contains strong the selecting with the culture medium of 150 μ g/ml Shi Taning of 1mg/ml and handles parallel 3 wares of every concentration.Put 37 ℃, 5%CO
2The constant temperature and humidity incubator cultivated 3 days, cell is diluted to 1 * 10 after with trypsinization
6/ ml, usefulness PBS centrifuge washing twice is with 4 ℃ of following fixedly 1h of 90% methanol PBS solution.After fixing, cell is through the centrifugal 5min of 1100g, and with ice PBS washing twice, the RNA enzyme is handled 10min.Subsequently, the freezing 10min of cell is behind bromination third pyridine (PI) dyeing 1.5min, with cells were tested by flow cytometry apoptosis and cell cycle.
Apoptotic index (AI)=apoptosis cell/total cell number
The influence of GZ concentration in the S pair cell of variable concentrations
From the result of the flow cytometry strong apoptosis that significantly to induce the carcinoma of gallbladder cell of selecting of 1mg/ml as can be seen.Behind 150 μ g/ml Shi Taning synergism, this apoptosis-induced effect is obviously strengthened, and is strong 1.8 times of selecting independent effect.See Fig. 3.
Determination of drug concentration in embodiment 3 cells
The drug treating process of cell is with the streaming cell analysis, after treating that drug treating finishes, handle with trypsinization, the centrifugal 10min collecting cell of 1000g, twice of reuse PBS centrifuge washing, every group adds 0.5ml distilled water supersound process 30min, and the centrifugal 10min of 14000g gets supernatant and detects intracellular drug level with high-efficient liquid phase technique (HPLC).Measure with the reverse post of Sb-C18, the proportion of mobile phase condition is 5% methanol and 95% water, detects 466nm special absworption peak down, and to go out peak area with it be that vertical coordinate is mapped.From the result of HPLC as can be seen in the drug combination group cell strong concentration of selecting select independent medication group apparently higher than strong, this show execute him would rather be to promote strong selecting to intracellular transport process.
See Fig. 4.
Claims (5)
1. mix preparation that strengthens the solid tumor cell chemosensitivity, it is characterized in that: this mix preparation is that a kind of medicine and a kind of period specific chemotherapeutics that influences the solid tumor cell cycle regulating got according to certain concentration ratio is mixed, the medicine that wherein influences the solid tumor cell cycle regulating is Shi Taning, and the period specific chemotherapeutics is selected for strong.
2. mix preparation as claimed in claim 1 is characterized in that: Shi Taning, strong selecting are dissolved in normal saline, strongly select concentration and are not higher than 3.5mg/ml, and Shi Taning concentration is not higher than 150 μ g/ml.
3. mix preparation as claimed in claim 2 is characterized in that: be good for the concentration of selecting with Shi Taning and be respectively, be good for and select 0.5～2.5mg/ml, execute his peaceful 62.5～150 μ g/ml.
4. the application in preparation treatment solid tumor cell medicine as claim 1 or 2 or 3 described mix preparations.
5. application as claimed in claim 4 is characterized in that: solid tumor cell is the carcinoma of gallbladder cell.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997005167A1 (en) * | 1995-07-28 | 1997-02-13 | Romano Deghenghi | Somatostatin-analogous cyclic peptides with inhibitory activity on growth hormone |
| CN1531441A (en) * | 2001-01-12 | 2004-09-22 | �о���Ӧ�ÿ�ѧЭ��ɷ�����˾ | Pharmaceutical composition for inhibiting vascular proliferation and method of use thereof |
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2005
- 2005-09-14 CN CNB2005100296232A patent/CN1317031C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997005167A1 (en) * | 1995-07-28 | 1997-02-13 | Romano Deghenghi | Somatostatin-analogous cyclic peptides with inhibitory activity on growth hormone |
| CN1531441A (en) * | 2001-01-12 | 2004-09-22 | �о���Ӧ�ÿ�ѧЭ��ɷ�����˾ | Pharmaceutical composition for inhibiting vascular proliferation and method of use thereof |
Non-Patent Citations (1)
| Title |
|---|
| 健择为主联合化疗治疗晚期恶性肿瘤的临床观察 仲琴，实用肿瘤学杂志，第15卷第3期 2001 * |
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