Targeting transient receptor potential canonical 1 reduces non‑small cell lung cancer chemoresistance and stemness via inhibition of PI3K/AKT signaling

Jiahui Jin; Xinyu Yan; Yaru Zhao; Haojie Zhang; Kai Zhuang; Yating Wen; Jingjing He; Junzhen Gao

doi:10.3892/ol.2023.13810

Targeting transient receptor potential canonical 1 reduces non‑small cell lung cancer chemoresistance and stemness via inhibition of PI3K/AKT signaling

Oncol Lett. 2023 Apr 13;25(6):224. doi: 10.3892/ol.2023.13810. eCollection 2023 Jun.

Authors

Jiahui Jin¹, Xinyu Yan², Yaru Zhao², Haojie Zhang², Kai Zhuang², Yating Wen², Jingjing He³, Junzhen Gao²

Affiliations

¹ Department of Oncology, Affiliated Qingdao Central Hospital, Qingdao University, Qingdao, Shandong 266042, P.R. China.
² Department of Respiratory and Critical Care Medicine, The Affiliated People's Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010050, P.R. China.
³ Department of Geriatrics, The Affiliated People's Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010050, P.R. China.

Abstract

TRPC1 enhances cell proliferation and migration in non-small cell lung cancer (NSCLC); however, its effect on NSCLC chemoresistance and stemness remains to be determined. The aim of the current study was to investigate the effect of TRPC1 on NSCLC chemoresistance and stemness and to determine the underlying mechanism of action. Cisplatin-resistant A549 (A549/CDDP) and H460 (H460/CDDP) cells were first established and were then transfected with negative control small interfering (si)RNA (si-NC) or TRPC1 siRNA (si-TRPC1). Cells were then treated with 740 Y-P, a PI3K/Akt agonist. Subsequently, the sensitivity of A549/CDDP and H460/CDDP cells to CDDP was evaluated. Furthermore, the expression levels of CD133 and CD44, and sphere formation ability were also determined. The results showed that the half-maximal inhibitory concentration (IC₅₀) of CDDP was significantly higher in A549/CDDP cells compared with A549 cells and in H460/CDDP cells compared with H460 cells. TRPC1 silencing decreased the IC₅₀ value of CDDP compared with the si-NC group in A549/CDDP (11.78 vs. 21.58 µM; P<0.01) and H460/CDDP (23.76 vs. 43.11 µM; P<0.05) cells. Additionally, TRPC1 knockdown in both cell lines decreased the number of spheres formed compared with the si-NC group. Furthermore, compared with the si-NC group, A549/CDDP cells transfected with si-TRPC1 exhibited decreased levels of both CD133 (P<0.01) and CD44 (P<0.05). However, only CD133 (P<0.05) was downregulated in TRPC1-depleted H460/CDDP cells compared with the si-NC group. In addition, TRPC1 knockdown repressed PI3K/AKT signaling compared with the si-NC group in both A549/CDDP and H460/CDDP cells (all P<0.05). Finally, cell treatment with 740 Y-P reversed the effect of TRPC1 knockdown on PI3K/AKT signaling, chemoresistance, and cancer stemness in A549/CDDP and H460/CDDP cells (all P<0.05). In conclusion, the results of the current study suggested that targeting TRPC1 could attenuate cancer stemness and chemoresistance via suppression of PI3K/AKT signaling in NSCLC.

Keywords: PI3K/AKT signaling; chemoresistance; non-small cell lung cancer; stemness; transient receptor potential canonical 1.

Grants and funding

This study was supported by the Beijing Medical Award Foundation of China (grant no. YXJL-2020-0785-0178).