Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
Cancer Lett. 2013 Jun 10;333(2):152-8. doi: 10.1016/j.canlet.2013.01.002. Epub 2013 Jan 20.
Hedgehog signaling plays critical roles in drug resistance of PDAC. We demonstrate that SHH is highly expressed in PDAC patients and cell lines. SHH signaling protects PDAC cells against gemcitabine induced apoptosis, because either over-expression or knockdown of SHH in PDAC cells affects the sensitivity to gemcitabine. Mechanistic studies show that ABCB2 serves as the downstream target of SHH signaling, leading to the drug resistance of PDAC cells. Combinational treatments with gemcitabine and cyclopamine yield synergistic antitumor effects in vitro and in vivo. Our study suggests that inhibiting SHH signaling or targeting ABCB2 gene improves the efficacy of chemotherapy in patients with PDAC.
Hedgehog 信号通路在 PDAC 的耐药性中发挥着关键作用。我们证实 SHH 在 PDAC 患者和细胞系中高度表达。SHH 信号通路保护 PDAC 细胞免受吉西他滨诱导的细胞凋亡，因为 PDAC 细胞中 SHH 的过表达或敲低会影响对吉西他滨的敏感性。机制研究表明，ABCB2 是 SHH 信号通路的下游靶标，导致 PDAC 细胞的耐药性。吉西他滨与环巴胺联合治疗在体外和体内均产生协同抗肿瘤作用。我们的研究表明，抑制 SHH 信号通路或靶向 ABCB2 基因可提高 PDAC 患者化疗的疗效。
