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Lobaplatin promotes radiosensitivity, induces apoptosis, attenuates cancer stemness and inhibits proliferation through PI3K/AKT pathway in esophageal squamous cell carcinoma.

S. Pan,Yuchen Sun,Donghu Sui,Tian Yang,Shenbo Fu,Jizhao Wang,B. Hui,Ruxing Xi,Chenchen He,Xiaozhi Zhang

Published 2018 in Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

ABSTRACT

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 anti-tumor 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.

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