Ultra-violet irradiation induces apoptosis via mitochondrial pathway in pancreatic cancer cells
Ultra-violet irradiation induces apoptosis via mitochondrial pathway in pancreatic cancer cells
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DOI：
10.3892/ijo.2011.1188
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发表时间：
2011-12-01
影响因子：
5.2
通讯作者：
Moriwaki, Hisataka
中科院分区：
文献类型：
--
作者：
Yamauchi, Takahiro;Adachi, Seiji;Moriwaki, Hisataka
胰腺癌是一种高度致命的疾病，吉西他滨被认为是晚期胰腺癌治疗的标准治疗方案。然而，患者使用吉西他滨治疗的结果仍然不令人满意，需要进一步开发新的治疗方法。我们最近发现，短波长紫外线（UV-C）通过下调人胰腺癌细胞的表皮生长因子受体（EGFR）来抑制细胞增殖，而在正常胰腺上皮（PE）细胞中则没有这种作用。在这项研究中，我们研究了UV-C对几种来源于胰腺的细胞系细胞凋亡的影响。在Panel、MiaPaca2、KP3和BxPC3胰腺癌细胞中，UV-C诱导多adp核糖聚合酶（PARP）裂解，这是细胞凋亡的标志，但在PE细胞中没有。我们在Hoechst 33258染色中也观察到类似的效果，显示DNA片段化。虽然肿瘤抑制蛋白p53在UV-C诱导的细胞损伤中起关键作用，但我们没有观察到对UV-C的敏感性与p53状态之间的相关性。Thapsigargin，一种通过消耗腔内钙储存来促进内质网（ER）应激的药物，以及顺式二胺铂（II）二氯化，一种经典的导致DNA损伤的抗癌药物，甚至在PE细胞中诱导PARP切割。此外，uv - c诱导的Panel和KP3细胞凋亡与细胞色素c的释放相关，表明其通过线粒体途径介导。综上所述，UV-C对胰腺癌细胞具有强大的抗癌作用，而对正常细胞没有不良影响，可能对治疗人类胰腺癌有用。
Pancreatic cancer is a highly lethal disease and gemcitabine is considered to be the standard of care for the treatment of advanced pancreatic cancer. However, the outcome of the patients treated with gemcitabine is still unstatisfactory and further development of new treatments is required. We recently found that short wavelength ultra-violet (UV-C) suppresses cell proliferation with downregulation of epidermal growth factor receptor (EGFR) in human pancreatic cancer cells, but not in normal pancreatic epithelial (PE) cells. In this study, we investigated the effect of UV-C on apoptosis in several cell lines derived from the pancreas. UV-C induced poly(ADP-ribose) polymerase (PARP) cleavage, which is a marker of cells undergoing apoptosis, in Panel, MiaPaca2, KP3 and BxPC3 pancreatic cancer cells, but not in PE cells. We also observed similar effects in Hoechst 33258 staining, which shows DNA fragmentation. While p53, a tumor suppressor protein, plays a critical role in UV-C-induced cell damage, we did not observe the correlation between the sensitivity to UV-C and p53 status. Thapsigargin, an agent that promotes endoplasmic reticulum (ER) stress by depletion of lumenal calcium stores, as well as cis-diamineplatinum (II) dichloride, a classical anti-cancer drug that causes DNA damage, induced PARP cleavage even in PE cells. Moreover, UV-C-induced apoptosis in Panel and KP3 cells was associated with the release of cytochrome c, indicating that it was mediated via mitochondrial pathway. Taken together, UV-C has a potent anti-cancer effect on pancreatic cancer cells without adverse effect on normal cells and it could be useful for the treatment of human pancreatic cancers.