Li Li, Chen Cheng, Xiang Qin, Fan Songqing, Xiao Tian, Chen Yangchao, Zheng Duo
Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen University International Cancer Center, Department of Cell Biology and Genetics, School of Medicine, Shenzhen University, Shenzhen, China.
Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, China.
Front Oncol. 2022 Mar 25;12:773654. doi: 10.3389/fonc.2022.773654. eCollection 2022.
Approximately 85% of lung cancer cases are non-small-cell lung cancer (NSCLC). Chemoresistance is a leading cause of chemotherapy failure in NSCLC treatment. Transient receptor potential cation channel subfamily V, member 1 (TRPV1), a non-selective cation channel, plays multiple roles in tumorigenesis and tumor development, including tumor cell proliferation, death, and metastasis as well as the response to therapy. In this study, we found TRPV1 expression was increased in NSCLC. overexpression induced cisplatin (DDP) and fluorouracil (5-FU) resistance in A549 cells independent of its channel function. TRPV1 expression was upregulated in A549-DDP/5-FU resistant cells, and DDP/5-FU sensitivity was restored by knockdown. overexpression mediated DDP and 5-FU resistance by upregulation of drug transporter gene expression, thereby increasing drug efflux, enhancing homologous recombination (HR) DNA repair pathway to alleviate apoptosis and activating IL-8 signaling to promote cell survival. These findings demonstrate an essential role of TRPV1 in chemoresistance in NSCLC and implicate TRPV1 as a potential chemotherapeutic target.
大约85%的肺癌病例是非小细胞肺癌（NSCLC）。化疗耐药是NSCLC治疗中化疗失败的主要原因。瞬时受体电位阳离子通道亚家族V成员1（TRPV1）是一种非选择性阳离子通道，在肿瘤发生和肿瘤发展中发挥多种作用，包括肿瘤细胞增殖、死亡和转移以及对治疗的反应。在本研究中，我们发现NSCLC中TRPV1表达增加。其过表达在A549细胞中诱导顺铂（DDP）和氟尿嘧啶（5-FU）耐药，且与通道功能无关。TRPV1在A549-DDP/5-FU耐药细胞中表达上调，敲低TRPV1可恢复DDP/5-FU敏感性。TRPV1过表达通过上调药物转运蛋白基因表达介导DDP和5-FU耐药，从而增加药物外排，增强同源重组（HR）DNA修复途径以减轻凋亡，并激活IL-8信号以促进细胞存活。这些发现证明了TRPV1在NSCLC化疗耐药中的重要作用，并表明TRPV1是一个潜在的化疗靶点。
