Nicotine enhances store‑operated calcium entry by upregulating HIF‑1α and SOCC components in non‑small cell lung cancer cells

Wang,Yan; He,Jianxing; Jiang,Hua; Zhang,Qi; Yang,Haihong; Xu,Xiaoming; Zhang,Chenting; Xu,Chuyi; Wang,Jian; Lu,Wenju

doi:10.3892/or.2018.6580

Nicotine enhances store‑operated calcium entry by upregulating HIF‑1α and SOCC components in non‑small cell lung cancer cells

Authors:
- Yan Wang
- Jianxing He
- Hua Jiang
- Qi Zhang
- Haihong Yang
- Xiaoming Xu
- Chenting Zhang
- Chuyi Xu
- Jian Wang
- Wenju Lu
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Affiliations: State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China
Published online on: July 17, 2018 https://doi.org/10.3892/or.2018.6580
Pages: 2097-2104

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Abstract

Store‑operated calcium entry (SOCE) is critical for regulating the proliferation and metastasis of various cancer types. The present study aimed to investigate the role of SOCE on nicotine‑promoted proliferation of non‑small cell lung cancer (NSCLC) A549 cells. Cell proliferation was evaluated by BrdU incorporation assay. The SOCE and basal [Ca2+]i in NSCLC A549 cells were determined using Fura‑2 fluorescence microscopy. The mRNA and protein expression levels were determined by real‑time quantitative PCR and western blotting, respectively. The results demonstrated that, in A549 cells, the detectable store‑operated calcium channel (SOCC) components were TRPC proteins 1, 3, 4 and 6 and Orail, among which TRPC1, TRPC6 and Orai1 are expressed at relatively high levels with TRPC3 and TRPC4 at relatively low levels. Nicotine upregulated the mRNA and protein expression of TRPC1, TRPC6 and Orai1, increased basal [Ca2+]i and enhanced SOCE. Promotion of cell proliferation but not migration was observed in the nicotine‑treated cells, which was inhibited by SOCE inhibitor SKF‑96365. Furthermore, nicotine upregulated HIF‑1α expression in the A549 and NCI‑H292 cells. Silencing of HIF‑1α abrogated the increases in TRPCs and Orail and reversed the increases in basal [Ca2+]i and SOCE. Meanwhile, suppression of proliferation was observed in cells following HIF‑1α silencing. In conclusion, the results indicate that nicotine promotes lung cancer cell proliferation likely by upregulating HIF‑1α and SOCC components and therefore enhancing SOCE and increasing basal [Ca2+]i.

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