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Research On900KYB Reversal Of Gastric Cancer Cell Multidrug Resistance Based On The Theory Of Stasis, Heat And Tonxin In Shang Han Lun

Posted on:2013-02-26Degree:MasterType:Thesis
Country:ChinaCandidate:H J ZhangFull Text:PDF
GTID:2234330374451340Subject:TCM clinical basis
Abstract/Summary:
Heatiness, blood stasis and toxin are closely related. Heat can combine with toxin, blood stasis can become toxin after accumulated for a period of time, in turn causing complicated pathological conditions, in which increased the abrupt nature of the disease, lingering and difficult to treat.In treatment, need to governance the exact nature of illness and the need to distinguish between its pros and cons, priorities, thus minimizing the principal contradiction.Heatiness in body can cause fluid deficiency, body fluid in turn causing formation of phlegm, also will lead to blood stasis, these formation of harmful fluid can become solid and condensed mass, lumps, nodules. The stages accumulation of fluid becoming mass is a pathological features in the body.<Shang Han Lun> has a large number of theories closely related between the heat, blood stasis and toxin (three Evils) and their interpretation and use in the treatment of the disease. By the theoretical discussion of the subject between the heat, blood stasis and toxin, it is known that stasis, heat and toxin combine in the formation of accumulation, with a complicated pathogenesis. At the same time, the formation of these three is closely related to the multidrug resistance pathological mechanisms of tumour.In addition, subject to further explore of the causes of tumour cell multidrug resistance and pathological mechanisms. Found that the resistance of tumour cells is an important factor leading to failure of chemotherapy. This mechanisms can be from numerous sources, it is known that the multidrug resistance mechanism such as high expression of P-glycoprotein (P-gp); drug metabolism, such as glutathione S-transferase enzyme detoxification enhancement; drug target change, such as reduced level of topoisomerase II; regulation of apoptosis. such as the lack of p53gene or mutation.At present, there are three measures for the multidrug resistance reversal, Western medicine reversal, the reversal of gene therapy and Chinese medicine reversal. Western medicine reversal agents can lead to major side effects, and efficacy is not sure, cannot be extended to large-scale applications clinically; gene therapy still remain at the level of laboratory studies, and there are no clinical studies reported. There are still some time away from clinical application:while Traditional Chinese medicine is just the opposite, herbal effects are more gentle. less toxicity. and more studies have shown that some Traditional Chinese medicine reducing toxicity of chemotherapy with high efficiency and low toxicity, thus more possible to find from traditional Chinese medicine a MDR reversal agents.Based on this research, we selected ordinary human gastric cancer cell SGC7901and resistant cell SGC7901/DDP. The SGC7901/DDP cells are induced by the amount of cisplatin (DDP). more apparent tolerance to DDP. can continue proliferation in culture medium containing0.5mg L-1with cisplatin to doxorubicin hormone, vincristine produced significant resistance, with significant multi-drug resistant characteristics. In this study, measured by MTT assay ordinary strains of SGC7901cells and their sensitivity resistant strains SGC7901/DDP cells to DDP treatment of SGC7901IC50is0.326mg-L-1, SGC7901/DDP IC50is1.571mg-L-1. DDP tolerance is4.82times that of SGC7901cells, which means SGC7901/DDP cells tolerance to DDP is in line with the resistant cell characteristics, indicating that this study has been successfully constructed and can be used as multidrug resistance cell model. And then determination by900KYB anti-inflammatory pill intervention of tumor cell cytotoxicity study found that when the900KYB concentration of1x10-5g· ml-1. the survival of SGC7901SGC7901/DDP cells is91.49%and94.26%respectively, indicating KYB dosage is just right for SGC7901and SGC7901/DDP cells without apparent toxicity.Therefore, to determine. the KYB non-cytotoxic drug concentration, observation KYB intervention in gastric cancer cell multidrug resistance of the effect and mechanism of concentration of1x10-5g· ml-1KYB synergistic effect with DDP, the DDP intervention in SGC7901/DDP cells with an IC50dropped to0.374mg· L-1, which shows that the KYB may reduce the drug-resistant cells SGC7901/DDP survival rate, increasing its sensitivity to DDP. On the other hand, KYB also has a sensitizing effect on ordinary cell SGC7901, sensitizing multiples of3.02.To further define KYB in achieving the effect on mechanism of the reversal of tumour cell multidrug resistance, this research focused on multidrug resistance of the key link in the P-gp over-expression of the relevant research. The process of multidrug resistance P-gp over-expression can lead to increased efflux of anticancer drugs to reduce the intracellular drug accumulation.Found by flow cytometry, SGC7901cells DDP has an average fluorescence intensity of 1035.71, SGC7901/DDP cells DDP has fluorescence intensity of327.76,3.16times lower than SGC7901cells (P <0.05); SGC7901cells P-gp expression positive rate was10.81%, SGC7901/DDP of P-gp expression positive rate was44.21%. significantly higher than the normal cell (P<0.01). Lower SGC7901/DDP cell drug resistance and intracellular DDP content with P-gp expression increased due to isolation of intracellular drug efflux.Study of900anti-inflammatory pill intervention DDP, SGC7901/DDP intracellular fluorescence intensity of the intervention was327.76being increased to658.79and SGC7901/DDP of P-gp expression is reduced to15.41%from44.21%, indicating that the KYB indeed can significantly reduce the resistant cell SGC7901/DDP P-gp expression, the antagonistic intracellular anticancer drug efflux of DDP. This may be one of the important effectors mechanism of anti-tumour process in the900anti-inflammatory pill to reverse the tumour cell multidrug resistance.
Keywords/Search Tags:blood stasis, heat, toxic syndrome governance theory, 900anti-inflammatory pill, gastric cancer cells, multidrug resistance, effect mechanism
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