冬凌草甲素逆转耐吉西他滨胰腺癌PANC-1／Gem细胞耐药性的研究

目的分析冬凌草甲素对耐吉西他滨胰腺癌PANC-1／Gem细胞的影响，探讨其逆转耐药的机制。方法诱导建立耐吉西他滨胰腺癌PANC-1／Gem细胞；CCK-8法检测吉西他滨对人胰腺癌PANC-1／Gem及PANC-1细胞增殖的影响；采用Chou—Talalay计算药物联合指数（CI）；Westernblot检测干预前后耐药相关蛋白的表达水平建立皮下异种移植瘤模型，观测不同药物组别对肿瘤生长情况的影响；免疫组化法检测不同组别移植瘤中相关耐药蛋白的变化差异。结果PANC-1／Gem细胞较PANC-1细胞对吉西他滨的敏感性降低（P〈0．01）；冬凌草甲素能明显抑制胰腺癌细胞增殖；冬凌草甲素与吉西他滨具有协同抗肿瘤作用；与空白组和吉西他滨组比较，冬凌草甲素及联合组中MRP1和GST—π表达量降低；冬凌草甲素对移植瘤具有抑制作用且能够降低移植瘤中MRP1蛋白的表达。结论冬凌草甲素在体内外能够抑制人耐吉西他滨胰腺癌PANC-1／Gem细胞的增殖，通过降低MRP1及GST-π耐药蛋白的表达逆转PANC-1／Gem对吉西他滨的耐药，增强其对吉西他滨的敏感性。

Objective To observe the effect of oridonin on gemcitabine-resistant pancreatic cancer PANC-1/Gem cells, and to explore its mechanism of reversal of drag resistance. Method The gemcitabine-resistant pancreatic cancer PANC-1/Gem cell lines were established. The contents of gemcitabine on the proliferation of human pancreas cancer cells PANC-1/Gem and PANC-1 were detected by CCK-8 method. Chou-Talalay was used to calculate the drug combination index （ CI ） . The drug resistance proteins expression level were detected by Western blot. The subcutaneous xenograft model was established and the effects of different drug groups on tumor growth were observed. Immunohistochemistry were used to detect drug resistance proteins in different groups of tumors. Result PANC-1/Gem cells were less sensitive to gemcitabine than PANC-1 cells （P〈0.01） . There was no significant difference in the proliferation inhibition rate of the two cell lines. A synergistic anti-tumor effect was found in the oridonin and gemcitabine. Compared with the blank group and the gemcitabine group, oridonin and joint group suppressed the expression of MRP1 and GST- π protein. Oridonin inhibited the growth of tumors and downregnlated the expression of MRP1 proteins in transplantation tumor. Conclusion Oridonin inhibits the prohferation of gemcitabine-resistant PANC-1/Gem cells in vitro and in vivo. Oridonin can reverse the resistance of gemcitabine to PANC- 1/Gem and decrease its＇ sensitivity to gemcitabine by decreasing the expression of MRP1 and GST- π.