CN104586887A - Application of cis-platinum in preparation of medicine for inhibiting transfer and spread of tumor cells - Google Patents
Application of cis-platinum in preparation of medicine for inhibiting transfer and spread of tumor cells Download PDFInfo
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- CN104586887A CN104586887A CN201510068024.5A CN201510068024A CN104586887A CN 104586887 A CN104586887 A CN 104586887A CN 201510068024 A CN201510068024 A CN 201510068024A CN 104586887 A CN104586887 A CN 104586887A
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Abstract
The invention discloses an application of application of cis-platinum in preparing a medicine for inhibiting transfer and spread of tumor cells. The transfer capacity of tumor cells is inhibited by virtue of a medicine prepared from the cis-platinum, the cis-platinum is a low-toxicity medicine which is capable of taking a relatively high blocking effect in a tumor spread process, and at the same time, other related anti-tumor drugs are adopted for treatment, so that the mortality of normal cells is greatly reduced; while since most existing anti-tumor drugs are cytotoxic drugs, many normal cells die when tumor cells are killed.
Description
Technical field
The present invention relates to cisplatin in the new purposes of pharmaceutical field, be specifically related to the application of cisplatin in the medicine preparing inhibition tumor cell metastasis and extension.
Background technology
Cisplatin, foreign language abbreviation DDP, is the heavy metal complex that center combines with two chlorine atoms and two amino molecules with bivalence platinum, is similar to bifunctional alkylating agents, can suppresses the reproduction process of DNA.DDP cells being most sensitive, suppresses RNA and protein synthesis during high concentration.Cisplatin, to anoxic cell effect, may diffuse through charged cell membrane after entering human body.Think at present, DDP Main Function position is at the purine of DNA and pyrimidine bases.Effect and purposes: cisplatin belongs to cell cycle nonspecific agent (CCNSA), has cytotoxicity, can the DNA replication dna process of anticancer, and damages structure on its cell membrane, has stronger broad spectrum anticancer effect.
DDP has that anticancer spectrum is wide, effect is strong, have synergism with multiple antineoplastic agent and without features such as crossing drug resistants, clinically all can show curative effect for multiple entity tumors such as ovarian cancer, carcinoma of prostate, carcinoma of testis, pulmonary carcinoma, nasopharyngeal carcinoma, esophageal carcinoma, malignant lymphoma, G. cephalantha, thyroid carcinoma and osteogenic sarcomas.
For treating a line medication of multiple solid tumor.(EP scheme) is combined for treatment SCLC or NSCLC mono-line scheme with VP-16, combined with MMC, IFO(IMP scheme), or the scheme such as NVB is treatment NSCLC common scheme, combined chemotherapy based on DDP is also the primary treatment scheme of advanced ovarian cancer, osteosarcoma and neuroblastoma, effective to multiple location squamous cell carcinoma, transitional cell carcinoma with the coupling such as ADM, CTX, as incidence, cervix uteri, esophagus and urological cancer etc.
Other pharmacological actions of cisplatin are not yet found in existing open source literature.
Summary of the invention
Goal of the invention: the object of the invention is to provide the application of a kind of cisplatin in the medicine preparing inhibition tumor cell metastasis and extension.
Technical scheme: the application of cisplatin in the medicine preparing inhibition tumor cell metastasis and extension.
Preferably, described tumor cell is colon cancer cell.
Preferably, wherein the concentration of cisplatin is 5uM ~ 10uM.
Inventor be experimental studies have found that by cell aspect, and the transfer ability of cisplatin to tumor cell has certain inhibitory action.Current is intravenous injection or intravenous drip for qualitative its of existing indication: each 20 ~ 30mg or 20mg/m
2, be dissolved in the injection of normal saline 20 ~ 30ml medium-sized vein, or be dissolved in 5% glucose injection 250 ~ 500ml iv drip, splanchnocoel is injected: 1 time on the 7th ~ 10, thoracic cavity, each 30 ~ 60mg.Each 100 ~ the 160mg in abdominal cavity.Intra-arterial injection: each 20 ~ 30ml, in injected by intubate, being used in conjunction 5 was 1 cycle, and interval can be repeated for 3 weeks.Arterial perfusion is mainly used in tumor of head and neck.
It is reference frame that the present invention needs according to existing preparation instructions of taking, and existing cell aspect experiment basis determines new clinical administration and dosage according to new indication curative effect and the design of follow-up related experiment.
The present invention by after tumor cell collection is cultivated, recycling medicine irritation cell, observation of cell form the area of quantitative analysis cell layer, namely cell can with the area of other cells contacting, thus judge the diffusivity of tumor cell.Cellular layer area is more conducive to being formed with other cells being connected more greatly.Cell migration needs the cooperation of internal and external factor.Outside factor refers to extracellular signaling molecule.Internal factor is the signal transducting system of phalangeal cell and the cytoskeleton of execution motion and molecular motor then, also has the various molecules participating in talin formation.Extracellular signal needs endocellular signal molecule relay after completing its mission in conjunction with after birth receptor, movable information is passed to further the executable unit of cell migration---cytoskeleton and molecular motor.Miscellaneous endocellular signal molecule can interact, and affects the distribution of these two kinds of molecules aftermentioned, structure and activity, reaches the object of intense adjustment cell movement.As can be seen here, the transfer of tumor cell, and the close relation between cell itself and cell.
Cancerous cell is compared with its homology normal structure, and intercellular cohesiveness reduces, therefore cancerous cell easily disperses in vivo and shifts.Normal cell outer by fibronectin be a kind of extracellular adhesive glycoprotein, it enhance the adhesion between cell and extracellular matrix.The fibronectin of cancerous cell significantly reduces or lacks, and obstacle occurs in cadherin synthesis, thus destroys the adhesion between cell and substrate and between cell and cell, and therefore cancerous cell has the attribute being easy to invade profit tissue and transfer.The increase contact area enhanced between each cell of the area of cancerous cell is more conducive to adhesion each other and attachment.
Cause although the transfer of tumor cell is formed jointly by many factors, but with the area of cellular layer, namely cell can with the foundation of the area of other cells contacting as cell transfer ability size, in this, as the method for measuring of Cell tracking intensity, there is the advantage that with low cost, easy and simple to handle, result is easily sentenced, the cell area that it shows increases the most directly observation and distinguishes, after mainly being stimulated by dosing exactly, immunostaining is carried out to Cell tracking molecule E-cadherin protein, then carry out quantitative assay.Cellular layer area is more conducive to being formed with other cells being connected more greatly.
The present invention thinks that cisplatin is experimental subject, and its merit rating shifted at inhibition tumor cell is considered in assessment.Main Basis is changed to specifically with cell area before and after medicine irritation.
Beneficial effect: 1, the transfer ability of the present invention's drug on tumor cell of utilizing cisplatin to prepare suppresses, cisplatin is low cytotoxic drug, larger blocking effect can be played in tumor diffusion process, meanwhile adopt other related neoplasms medicines to treat again, Normocellular mortality can be reduced in a large number; And existing tumour medicine mostly is cell toxicity medicament, while killing tumor cell, a large amount of normal cell is also dead together; 2, cisplatin used in the present invention is into the existing medical compounds of Drug Storage, and the R&D cycle can obviously reduce compared with the cycle of new drug development.
Accompanying drawing explanation
Fig. 1 is the colon cancer cell figure after 0.5uM concentration cisplatin treated;
Fig. 2 is the colon cancer cell figure after 1uM concentration cisplatin treated;
Fig. 3 is the colon cancer cell figure after 5uM concentration cisplatin treated;
Fig. 4 is the colon cancer cell figure after 100uM concentration cisplatin treated;
Fig. 5 is positive controls, by the colon cancer cell figure after 10 uM concentration nocodazole process;
Fig. 6 is negative control group.
Detailed description of the invention
Below by accompanying drawing, technical solution of the present invention is described in detail, but protection scope of the present invention is not limited to described embodiment.
embodiment 1:cisplatin suppresses the application in the medicine of colon cancer cell metastasis and extension in preparation.Specific experiment scheme is as follows:
1, experiment material
That the experimental stage of the present invention adopts is colon cancer cell (HT29), and the medicine that positive control adopts is nocodazole (experimental concentration is 10uM).Negative control group is not through any process.
Wherein experiment adopts cis-Platinum compound Cl
2h
6n
2pt, CAS NO. is 15663-27-1, and concentration is respectively 10uM, 5uM, 1uM, 0.5uM.
2, experimental technique
To the cultivation colon cancer cell of 24 hours (cell density: 10
5) carry out medicine irritation process in 2 hours:
(1) by centrifugal for good for state in culture dish colon cancer cell, add appropriate culture fluid and make cell suspending liquid;
(2) obtained cell suspension counting, according to 10
5density add in 24 porose discs, put into the CO of 37oC
2cultivate in incubator;
After (3) 24 hours, change liquid, the cis-Platinum compound adding respective amount in culture fluid is configured to experiment desired concn, and positive control medicine, then continues cultivation 2 hours;
(4) cultivate after 2 hours and cell 37oC under the PFA solution of 2% is fixed 10 minutes, then carry out fluorescence staining.
3, experimental result process
Observe the colon cancer cell after fluorescence staining, the picture Image J process of observation is calculated the data of its cell area before and after dosing, and Ratio is the ratio of experimental group and negative control group.The results are shown in Table 1.
Table 1 cisplatin is to the size of HT29 cytositimulation after 2 hours
| 10uM | 5uM | 1uM | 0.5uM | Positive control | Negative control | |
| Individual cells average area | 6906.04 | 12367.4 | 6234.61 | 8429.48 | 5457.38 | 4844.17 |
| Ration | 142.56% | 255.30% | 128.70% | 174.01% | 112.66% | - |
Prove through experimental data, cisplatin makes the obvious scaling up of colon cancer cell surface area under concentration 5uM, and wherein effect is 5uM ~ 10uM preferably, proves that cisplatin can suppress the application in the medicine of colon cancer cell metastasis and extension in preparation.
embodiment 2:transwell Cell migration assay measures cisplatin to be affected colon cancer cell transfer ability.
By 1 × 10
5hT29 cell be seeded in Transwell cell, bottom adopts 12.0 μm of films, continue cultivate.After cell attachment, upper strata cell adds the DMEM complete medium of variable concentrations cisplatin, for maintaining osmotic pressure, need add 0.05%-0.2% BSA, and bottom chamber adds the DMEM complete medium containing 15%FBS and continues to cultivate 24h.Carefully wipe with cotton swab the cell that migration does not occur film upper surface, the cell migrating to film lower surface dyes with Giemsa after 37oC fixes 10 minutes through 2%PFA.Random selecting 10 visuals field under high power microscope, counting migrating cell.
Cell migration rate=[experimental group cell number meansigma methods/blank group cell number meansigma methods] × 100%.
The effect that result display cis-Platinum compound has the suppression of dose dependent to move to colon cancer cell HT29, compares migrating cell relative percentages and significantly reduces (P < 0.05) with matched group.In table 2.
Table 2 Transwell method detects cisplatin to the impact (n=3 x ± s) of HT29 cell migration
| Blank | 0.5μM | 1μM | 5μM | 10μM | |
| HT29（%） | 100±3.19 | 28.65±3.58 | 31.24±2.51 | 15.23±2.78 | 21.35±3.69 |
embodiment 3:injury repairing experiment detects cisplatin to tumor cell migration capacity.
Take the logarithm the HT29 cell of trophophase, in 24 orifice plates, every hole adds cell 1 × 10
5, grow up to after monolayer until cell, draw " one " font cut, PBS rinses, and matched group and experimental group add cisplatin variable concentrations respectively and take pictures, and after cultivating 22h, take pictures again in same position, measures migration distance.Experiment repetition 3 times, cell migration rate=[(experimental group 0h meansigma methods-experimental group 22h meansigma methods)/(blank group 0h meansigma methods-blank group 22h meansigma methods)] × 100%.
Cisplatin (0.5-10 μ g/ml) under variable concentrations detects the suppression migration after LTEP, A549 cytosis 22h, the effect that result display cisplatin has the suppression of dose dependent to move to colon cancer cell HT29.Compare cell mobility significantly to reduce (P < 0.05) with matched group.In table 3.
The experiment of table 3 injury repairing detects cisplatin to colon cancer cell HT29 mobility impact (n=3 x ± s)
| Blank | 0.5μM | 1μM | 5μM | 10μM | |
| HT29（%） | 100±4.25 | 30.87±4.62 | 35.49±3.06 | 18.23±3.62 | 25.29±2.47 |
Conclusion: cisplatin significantly can suppress the migration of colon cancer cell, can be used for inhibitor against colon carcinoma cells diversion medicaments of curing the disease.
As mentioned above, although represented with reference to specific preferred embodiment and described the present invention, it shall not be construed as the restriction to the present invention self.Under the spirit and scope of the present invention prerequisite not departing from claims definition, various change can be made in the form and details to it.
Claims (3)
1. the application of cisplatin in the medicine preparing inhibition tumor cell metastasis and extension.
2. application according to claim 1, wherein tumor cell is colon cancer cell.
3. application according to claim 1, wherein the concentration of cisplatin is 5uM ~ 10uM.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1832293A1 (en) * | 2004-12-10 | 2007-09-12 | TMRC Co., Ltd. | Remedy for cancer metastasis and cancer metastasis inhibitor |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1832293A1 (en) * | 2004-12-10 | 2007-09-12 | TMRC Co., Ltd. | Remedy for cancer metastasis and cancer metastasis inhibitor |
Non-Patent Citations (1)
| Title |
|---|
| 王炼等: "重组人内皮抑素腺病毒联合顺铂对小鼠结肠癌肺转移治疗作用研究", 《四川大学学报(医学版)》 * |
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