The inhibition of heme oxygenase-1 enhances the chemosensitivity and suppresses the proliferation of pancreatic cancer cells through the SHH signaling pathway
The inhibition of heme oxygenase-1 enhances the chemosensitivity and suppresses the proliferation of pancreatic cancer cells through the SHH signaling pathway
复制标题
抑制血红素加氧酶-1通过SHH信号通路增强化疗敏感性并抑制胰腺癌细胞增殖
DOI：
10.3892/ijo.2018.4363
复制
发表时间：
2018-06-01
影响因子：
5.2
通讯作者：
Wang, Zheng
中科院分区：
文献类型：
--
作者：
Han, Liang;Jiang, Jie;Wang, Zheng
胰腺癌（PC）是一种由于预后不良和对治疗的抵抗而导致高死亡率的癌症。血红素加氧酶-1（HO-1）在许多类型的癌症中显著过表达，并且似乎在癌症进展中起重要作用。在这项研究中，我们研究了HO-1对PC细胞增殖和对吉西他滨（Gem）敏感性的潜在影响。此外，还研究了音刺猬（SHH）信号通路在HO-1对PC进展的调节作用中的作用。为此，HO-1的表达在培养的PC细胞检测实时PCR，蛋白质印迹分析和免疫荧光。用针对HO-1的小干扰RNA或过表达质粒转染MIA PaCa-2和PANC-1细胞系以调节HO-1的表达。MTT法检测不同处理对细胞增殖的影响。结果显示HO-1在不同PC细胞中的表达差异显著。HO-1的过表达可诱导PC细胞增殖，而HO-1的抑制可降低PC细胞的增殖能力。此外，HO-1激活PC细胞中的SHH信号通路。此外，SHH信号通路被发现在HO-1诱导的PC细胞增殖中发挥作用。HO-1的抑制增强PC细胞对Gem的反应性，Gem被发现调节HO-1的表达和SHH通路的激活。总的来说，我们的研究结果表明，HO-1在PC细胞中的过表达可能是负责增加细胞增殖和抗癌治疗的抗性。HO-1激活的SHH信号通路可能是这一过程的内源性机制之一。我们的数据揭示了PC细胞中HO-1和SHH之间的关联，并可能有助于开发治疗PC患者的新治疗靶点。
Pancreatic cancer (PC) is a type of cancer associated with a high fatality rate due to a poor prognosis and resistance to treatment. Heme oxygenase-1 (HO-1) is significantly over-expressed in a number of types of cancer and seems to play an important role in cancer progression. In this study, we examined the potential effects of HO-1 on PC cell proliferation and sensivity to gemcitabine (Gem). Furthermore, the role of the sonic hedgehog (SHH) signaling pathway in the regulatory effects of HO-1 on PC progression were examined. For this purpose, the expression of HO-1 was examined in cultured PC cells by real-time PCR, western blot analysis and immunofluorescence. Transfection with small interfering RNA against HO-1 or an overexpression plasmid were used to regulate the expression of HO-1 in the MIA PaCa-2 and PANC-1 cell lines. Cell proliferation was examined by MTT assays in response to the different treatments. The results revealed that HO-1 expression differed significantly in the different PC cells. The overexpression of HO-1 induced PC cell proliferation and the inhibition of HO-1 decreased the cell proliferative ability. Furthermore, HO-1 activated the SHH signaling pathway in the PC cells. In addition, the SHH signaling pathway was found to play a role in HO-1-induced PC cell proliferation. The inhibition of HO-1 enhanced the responsiveness of PC cells to Gem and Gem was found to regulate the expression of HO-1 and the activation of the SHH pathway. On the whole, our findings indicate that HO-1 overexpression in PC cells may be responsible for the increased cell proliferation and the resistance to anticancer therapy. Furthermore, the SHH signaling pathway, the activation of which was initiated by HO-1, may be one of the endogenous mechanisms in this process. Our data shed light into the association between HO-1 and SHH in PC cells, and may aid in the development of novel therapeutic targets for the treatment of patients with PC.