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目的:研究复方五味子素B对结肠癌耐药细胞株THC-8307/OXA的逆转作用及其作用机制。方法:采用MTT比色法检测奥沙利铂(OXA)和复方五味子素B(γSC)的细胞毒性;碱性磷酸酶免疫组织化学法和Western blot检测γSC对THC-8307/OXA细胞MRP1蛋白水平的影响。结果:γSC(6.0,12.5,25mg·L-1)对人结肠癌细胞(THC-8307)和耐奥沙利铂人结肠癌细胞(THC-8307/OXA)无显著毒性作用,OXA对THC-8307的IC50为0.06mg·L-1,对THC-8307/OXA的IC50为2.32mg·L-1,THC-8307/OXA较THC-8307对OXA耐药39倍,γSC(6.0,12.5,25mg·L-1)能使OXA对THC-8307/OXA细胞的IC50从2.32mg·L-1依次下降至0.370,0.128,0.057mg·L-1,逆转倍数分别为6.2,18.1,40.7倍。碱性磷酸酶免疫组织化学法和Western blot检测γSC(12.5mg·L-1)处理48h后,THC-8307/OXA细胞MRP1表达明显降低。结论:γSC具有逆转耐奥沙利铂人结肠癌细胞的MDR作用,其作用机制与下调MRP1表达有关。
Objective: To study the reversal effect and mechanism of compound Schisandrin B on colon cancer drug-resistant cell line THC-8307 / OXA. Methods: MTT assay was used to detect the cytotoxicity of oxaliplatin (OXA) and compound schisandrin B (γSC). The alkaline phosphatase immunohistochemical method and Western blot were used to detect the effect of γSC on MRP1 protein level in THC-8307 / OXA cells Impact. Results: There was no significant toxic effect of γSC (6.0,12.5,25 mg · L-1) on THC-8307 and THC-8307 / OXA cells. The effect of OXA on THC- 8307 had the IC50 of 0.06 mg · L-1, IC50 of THC-8307 / OXA was 2.32 mg · L-1, THC-8307 / OXA was 39 times more resistant to OXA than THC-8307, γSC (6.0,12.5,25 mg · L-1) decreased the IC50 of OXA to 0.370, 0.128 and 0.057 mg · L-1 from 2.32 mg · L-1 to THC-8307 / OXA cells respectively. The expression of MRP1 in THC-8307 / OXA cells was significantly reduced by alkaline phosphatase immunohistochemistry and Western blot detection of γSC (12.5mg · L-1) for 48h. CONCLUSION: γSC can reverse the MDR effect of oxaliplatin-resistant human colon cancer cells and its mechanism may be related to the down-regulation of MRP1 expression.