Lobaplatin promotes radiosensitivity, induces apoptosis, attenuates cancer stemness and inhibits proliferation through PI3K/AKT pathway in esophageal squamous cell carcinoma
Lobaplatin promotes radiosensitivity, induces apoptosis, attenuates cancer stemness and inhibits proliferation through PI3K/AKT pathway in esophageal squamous cell carcinoma
复制标题
洛铂通过 PI3K/AKT 通路促进食管鳞状细胞癌的放射敏感性、诱导细胞凋亡、减弱癌症干性并抑制增殖
DOI:
10.1016/j.biopha.2018.03.109
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发表时间:
2018-06-01
影响因子:
7.5
通讯作者:
Zhang, Xiaozhi
中科院分区:
文献类型:
--
作者:
Pan, Shupei;Sun, Yuchen;Zhang, Xiaozhi
Radiotherapy is one of the common treatments for esophageal squamous cell carcinoma (ESCC). Yet, local recurrence led by radioresistance is still not solved. Lobaplatin (LBP) is known to have powerful clinical antitumor activities in various tumors, but its effect in radiotherapy is rarely studied. Here we report that LBP is a promising radiosensitizer for ESCC. We treated ESCC cells with LBP and radiation, both separately and in combination. Untreated cells were set as control groups. We found that LBP inhibited ESCC cell growth and enhanced their radiosensitivity. LBP also impeded the tumor growth in vivo. LBP combined with radiation significantly increased ESCC cell apoptosis. Meanwhile, LBP obviously decreased the expression of cancer stem cells biomarker CD271 both in vitro and in vivo. The molecular mechanism was related to the downregulation of Bcl-2/Bax ratio, PI3K and p-AKT (Ser473) expression. Taken together, our findings indicated that LBP could enhance the radiosensitivity of ESCC cells by increasing radiation-induced apoptosis, attenuating cancer stemness and inhibiting PI3K/AKT pathway. These results provide a foundation for the combined therapy of radiation and LBP for ESCC in clinical practice.