Bmi1 inhibition enhances the sensitivity of pancreatic cancer cells to gemcitabine.
Bmi1 inhibition enhances the sensitivity of pancreatic cancer cells to gemcitabine.
复制标题
Bmi1抑制增强胰腺癌细胞对吉西他滨的敏感性
DOI：
10.18632/oncotarget.9293
复制
发表时间：
2016-06-14
期刊：
影响因子：
--
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Yin T;Zhang Z;Cao B;Duan Q;Shi P;Zhao H;Camara SN;Shen Q;Wang C
吉西他滨作为胰腺癌的标准治疗方案，由于化疗耐药，对胰腺癌患者的疗效有限。据报道，Bmi1的异常表达激活了多种生长调节通路，并赋予许多癌细胞抗凋亡的能力。然而，Bmi1在胰腺癌细胞对吉西他滨耐药反应中的作用仍然不清楚。在本研究中，我们发现一定剂量的吉西他滨可诱导胰腺癌细胞Bmi1的表达。Bmi1基因敲除可促进ROS的产生，增强吉西他滨的细胞毒作用。吉西他滨治疗时氧化应激增加，可破坏线粒体膜，降低线粒体膜电位，最终导致细胞凋亡。抑制BMI1还抑制了吉西他滨处理的胰腺癌细胞中NF-κB信号的激活和下游分子的表达。此外，我们在体内观察了Bmi1抑制使胰腺移植瘤对吉西他滨增敏。综上所述，我们的研究表明Bmi1可以通过增加氧化应激和抑制NF-κB信号通路降低胰腺癌细胞对吉西他滨的敏感性，因此Bmi1可能成为增敏胰腺癌细胞对化疗药物的一个有前途的靶点。
As the standard therapy for pancreatic cancer, gemcitabine shows limited efficacy in pancreatic cancer patients because of chemoresistance. Aberrant expression of Bmi1 has been reported to activate multiple growth-regulatory pathways and confer anti-apoptotic abilities to many cancer cells. However, the role of Bmi1 in response of pancreatic cancer cells towards gemcitabine resistance remains elusive. In this study, we found that certain dose of gemcitabine treatment induced Bmi1 expression in pancreatic cancer cells. Knockdown of Bmi1 enhanced ROS production and promoted the cytotoxic effect of gemcitabine. The increased oxidative stress upon gemcitabine treatment could disrupt mitochondrial membrane and decrease mitochondrial membrane potential, eventually leading to apoptosis. Bmi1 inhibition also suppressed the activation of NF-κB signaling and the expressions of downstream molecules in pancreatic cancer cells treated with gemcitabine. Moreover, we observed Bmi1 inhibition sensitized the pancreatic xenograft tumors to gemcitabine in vivo. Taken together, our study demonstrated that Bmi1 could decrease the sensitivity of pancreatic cancer cells to gemcitabine through increasing oxidative stress and inhibiting NF-κB signaling, thus Bmi1 may serve as a promising target for sensitizing pancreatic cancer cells to chemotherapy.
登录
查看更多内容
影响因子：
--
作者：
Suzuki S;Okada M;Shibuya K;Seino M;Sato A;Takeda H;Seino S;Yoshioka T;Kitanaka C
通讯作者：
Kitanaka C
DOI：
10.1155/2011/718302
发表时间：
2011
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Kim JH;Park SH;Kim YW;Ha JM;Bae SS;Lee GS;Cho SI;Choi BT;Shin HK
通讯作者：
Shin HK
影响因子：
3.3
作者：
Liou GY;Storz P
通讯作者：
Storz P
癌蛋白 Bmi-1 通过激活 IKK-核因子-kappaB 通路，对神经胶质瘤细胞产生凋亡抵抗。
影响因子：
6
作者：
Li, Jun;Gong, Li-Yun;Li, Mengfeng
通讯作者：
Li, Mengfeng
影响因子：
8.8
作者：
通讯作者：
--