The role of autophagy in the treatment of pancreatic cancer with gemcitabine and ionizing radiation
The role of autophagy in the treatment of pancreatic cancer with gemcitabine and ionizing radiation
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DOI：
10.3892/ijo_00000732
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发表时间：
2010-10-01
影响因子：
5.2
通讯作者：
Ku, Yonson
中科院分区：
文献类型：
--
作者：
Mukubou, Hideyo;Tsujimura, Toshiaki;Ku, Yonson
近年来，自噬已成为癌症治疗的重要机制。虽然吉西他滨和/或电离辐射是治疗胰腺癌的重要方式，但自噬在这种治疗中的作用尚未完全阐明。本研究探讨了自噬在吉西他滨和电离辐射治疗胰腺癌中的作用。为了评估吉西他滨和/或电离辐射对自噬的影响，我们使用了几种人胰腺癌细胞系。在体外和体内用吉西他滨和电离辐射治疗胰腺癌细胞产生协同细胞毒性。吉西他滨治疗后，自噬相关蛋白轻链3-II （LC3-II）上调。当吉西他滨联合电离辐射治疗时，LC3-II上调增强。此外，用吉西他滨和/或电离辐射处理的胰腺癌细胞的电镜检测到自噬的诱导。3-甲基腺苷阻断自噬表明自噬有助于吉西他滨治疗后细胞死亡并增强其细胞毒性。联合治疗后，自噬相关蛋白LC3和beclin-1的抑制作用和免疫反应性最强。综上所述，这些结果表明，吉西他滨和/或电离辐射可以激活胰腺癌细胞的自噬，激活的自噬在肿瘤抑制中起作用。这些发现可能对未来使用吉西他滨和电离辐射治疗胰腺癌的治疗策略具有重要意义。
Autophagy has recently emerged as a significant mechanism in cancer treatment. Although gemcitabine and/or ionizing radiation are important modalities in the treatment of pancreatic cancer, the contribution of autophagy in such treatment has not been fully elucidated. This study investigated the role of autophagy in the treatment of pancreatic cancer with gemcitabine and ionizing radiation. To evaluate the effect of gemcitabine and/or ionizing radiation on autophagy, several human pancreatic cancer cell lines were used. The treatment of pancreatic cancer cell cultures in vitro and in vivo with gemcitabine and ionizing radiation resulted in synergistic cytotoxicity. After treatment with gemcitabine, the autophagy-related protein light chain 3-II (LC3-II) was upregulated. When gemcitabine was combined with ionizing radiation treatment, LC3-II upregulation was enhanced. In addition, electron microscopy of pancreatic cancer cells treated with gemcitabine and/or ionizing radiation detected the induction of autophagy. The blockage of autophagy by 3-methyladenine indicated that autophagy contributed to cell death after gemcitabine treatment and enhanced its cytotoxicity. The inhibitory effect and immune reactivity of the autophagy-related proteins LC3 and beclin-1 were the strongest after the combination treatment. In conclusion, these results suggest that autophagy can be activated by gemcitabine and/ or ionizing radiation in the treatment of pancreatic cancer cells and that activated autophagy plays a role in cancer suppression. These findings may have important implications for future therapeutic strategies using gemcitabine and ionizing radiation against pancreatic cancer.