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

Pan, Shupei; Sun, Yuchen; Sui, Donghu; Yang, Tian; Fu, Shenbo; Wang, Jizhao; Hui, Beina; Xi, Ruxing; He, Chenchen; Zhang, Xiaozhi

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

Afiliación

Pan S; Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Sun Y; Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Sui D; GuiZhou EverGreen Pharmaceutical Company Limited, Guizhou, China.
Yang T; Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Fu S; Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Wang J; The Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Hui B; Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Xi R; The Fourth Department of Gynecological Tumor, The Shaanxi Province Oncology Hospital, Xi'an, Shaanxi, China.
He C; Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Zhang X; Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China. Electronic address: zhangxiaozhi@xjtu.edu.cn.

Biomed Pharmacother ; 102: 567-574, 2018 Jun.

Article en En | MEDLINE | ID: mdl-29597090

RESUMEN

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.

Asunto(s)

Apoptosis; Carcinoma de Células Escamosas/tratamiento farmacológico; Carcinoma de Células Escamosas/enzimología; Ciclobutanos/uso terapéutico; Neoplasias Esofágicas/tratamiento farmacológico; Neoplasias Esofágicas/enzimología; Células Madre Neoplásicas/patología; Compuestos Organoplatinos/uso terapéutico; Fosfatidilinositol 3-Quinasas/metabolismo; Proteínas Proto-Oncogénicas c-akt/metabolismo; Tolerancia a Radiación; Animales; Apoptosis/efectos de los fármacos; Carcinoma de Células Escamosas/patología; Línea Celular Tumoral; Proliferación Celular/efectos de los fármacos; Ciclobutanos/farmacología; Regulación hacia Abajo/efectos de los fármacos; Neoplasias Esofágicas/patología; Carcinoma de Células Escamosas de Esófago; Femenino; Humanos; Ratones Endogámicos BALB C; Ratones Desnudos; Células Madre Neoplásicas/efectos de los fármacos; Células Madre Neoplásicas/metabolismo; Proteínas del Tejido Nervioso; Compuestos Organoplatinos/farmacología; Tolerancia a Radiación/efectos de los fármacos; Receptores de Factor de Crecimiento Nervioso; Transducción de Señal/efectos de los fármacos; Regulación hacia Arriba/efectos de los fármacos; Proteína X Asociada a bcl-2/metabolismo

Palabras clave

Apoptosis; Cancer stem cells; Esophageal squamous carcinoma; Lobaplatin; PI3K; Radiosensitivity

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos Organoplatinos / Tolerancia a Radiación / Células Madre Neoplásicas / Neoplasias Esofágicas / Carcinoma de Células Escamosas / Apoptosis / Fosfatidilinositol 3-Quinasas / Ciclobutanos / Proteínas Proto-Oncogénicas c-akt Límite: Animals / Female / Humans Idioma: En Revista: Biomed Pharmacother Año: 2018 Tipo del documento: Article País de afiliación: China Pais de publicación: Francia

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