小白菊内酯增强PKC抑制剂诱导的人胃肠道间质瘤细胞系凋亡

Parthenolide enhances the apoptosis induced by PKC inhibitor in human gastrointestinal stromal tumors cell lines

目的探讨小白菊内酯(PTL)及蛋白激酶C抑制剂(PKC抑制剂)对人胃肠道间质瘤(GIST)细胞增殖和凋亡的影响及其机制。方法人GIST细胞系进行体外培养,用MTT法测GIST细胞增殖抑制率;用流式细胞技术检测GIST细胞的早期凋亡率;Western blot法检测GRP78与GADD153内质网应激相关蛋白的表达。实验分为对照组、PTL组、PKC抑制剂组及PTL和PKC抑制剂联合用药组。结果 PTL和PKC抑制剂联合用药对1)GIST细胞的抑制作用明显高于单独用药组(P<0.05);2)GIST细胞的早期凋亡率明显高于单独用药组(P<0.05);3)内质网应激相关蛋白GRP78与GADD153的表达明显高于单独用药组(P<0.05)。结论 PTL和PKC抑制剂联合用药促进GIST细胞凋亡,其机制与内质网应激途径介导的凋亡有关。

Objective To investigate the effect of parthenolide（ PTL） and PKC inhibitor on human gastrointestinal stromal tumor（ GIST） cell proliferation and apoptosis and the mechanism involved. Methods Human GIST cell lines were cultured in vitro,and the cell proliferation rate of GIST,was determinate by MTT; flow cytometry was used to test the early apoptosis rate of GIST; Western blot assay was applied to detect the expression of endoplasmic reticulum stress-related proteins,GRP78 and GADD153. There were four groups： control group,PTL group,PKC inhibitor group,combine PTL and PKC inhibitor group. Results PTL and PKC inhibitor combination therapy for GIST was significantly more effective than a single-drug therapy（ P〈0. 05）; as for the early apoptosis rate,the combination therapy for GIST cells was significantly higher than that medication alone group（ P〈0. 05）. the expression of endoplasmic reticulum stress-associated protein GRP78 and GADD153 was obviously higher in PTL and PKC inhibitor combination group than that in medication alone group（ P〈0. 05）. Conclusions PTL and PKC inhibitor combination therapy for GIST cells can induce apoptosis,which is possibly mediated via endoplasmic reticulum stress pathway.