Selective inhibition of PI3K110α as a novel therapeutic strategy for cetuximab-resistant oral squamous cell carcinoma

Selective inhibition of PI3K110α as a novel therapeutic strategy for cetuximab-resistant oral squamous cell carcinoma
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DOI:
10.3892/or.2020.7674
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发表时间:
2020-09-01
期刊:
影响因子:
4.2
通讯作者:
Umeda, Masahiro
Umeda, Masahiro
中科院分区:
医学3区
文献类型:
--
作者:
Tsuchihashi, Hiroki;Naruse, Tomofumi;Umeda, Masahiro

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IA 类 PI3K (PI3Kp110 α) 的 110 kDa 催化亚基的高表达可能在结直肠癌和头颈鳞状细胞癌表现出的西妥昔单抗耐药性中发挥重要作用。因此,本研究旨在探讨 PI3Kp110 α 通路中蛋白质的表达与西妥昔单抗耐药性之间的关联,以及 alpelisib(PI3K 抑制剂)和西妥昔单抗在口腔鳞状细胞癌(OSCC)细胞中的抗肿瘤作用。使用免疫组织化学确定 PI3Kp110 α 蛋白表达水平与肿瘤对西妥昔单抗的反应之间的关联。用alpelisib、西妥昔单抗或联合治疗OSCC细胞,并在体外和体内检查其效果。 PI3Kp110 α 蛋白表达与肿瘤对西妥昔单抗的反应显着相关(P
High expression of the 110 kDa catalytic subunit of the class IA PI3K (PI3Kp110 alpha) may play an important role in cetuximab resistance exhibited by both colorectal cancer and head and neck squamous cell carcinoma. Therefore, the present study aimed to examine the association between the expression of proteins in the PI3Kp110 alpha pathway and cetuximab resistance, and the antitumor effects of alpelisib (PI3K inhibitor) and cetuximab in oral squamous cell carcinoma (OSCC) cells. The association between PI3Kp110 alpha protein expression levels and the tumor response to cetuximab was determined using immunohistochemistry. OSCC cells were treated with alpelisib, cetuximab, or in combination, and the effects were examinedin vitroandin vivo. PI3Kp110 alpha protein expression was significantly associated with the tumor response to cetuximab (P