Shaohua Xu1, Hanchen Ma1, Yuhong Bo2, Mingju Shao3. 1. Department of Respiratory, The Second Hospital of Shandong University, Jinan 250033, Shandong Province, China. 2. Weihai Municipal Hospital, Weihai 264200, Shandong Province, China. 3. Department of Emergency Medicine, The Second Hospital of Shandong University, No. 247 Beiyuan Street, Jinan 250033, Shandong Province, China. Electronic address: sddxsmj@yeah.net.
Abstract
BACKGROUND: Several studies have verified the important role of cannabinoid and cannabinoid receptor agonists in tumor progression. However, little is known about the precise role of CB2 expression level in the progression of non-small-cell lung cancer (NSCLC). METHODS: The expression of CB2 in NSCLC tissues and corresponding paracancerous tissues was examined using immunohistochemical staining assay. The expression of CB2 was silenced by siRNA interference and loss-of-function assays were performed to investigate the biological function of CB2 in the proliferation, migration, invasion, and apoptosis of NSCLC cells. The expression of related proteins was detected using western blot analysis. RESULTS: In this study, we observed that CB2 was up-regulated in NSCLC tissues and the up-regulation was correlated with tumor size and advanced NSCLC pathological grading. Moreover, compared with the control group, silencing of CB2 decreased the proliferation, migration and invasion abilities of A549 and H1299 cells, and induced apoptosis by regulation of Bcl-2/Bax axis and active Caspase3. Furthermore, CB2 knockdown inactivated the Akt/mTOR/P70S6K pathway by decreasing the level of p-Akt, p-mTOR and expression of P70S6K in A549 and H1299 cells. CONCLUSION: Our data suggested that targeting CB2 may inhibit the growth and survival of NSCLC cells, which the Akt/mTOR/P70S6K pathway may be involved in. These results confer the pro-oncogenic role of CB2 in the progression of NSCLC, thus improving our understanding of CB2 in tumor progression.
BACKGROUND: Several studies have verified the important role of cannabinoid and cannabinoid receptor agonists in tumor progression. However, little is known about the precise role of CB2 expression level in the progression of non-small-cell lung cancer (NSCLC). METHODS: The expression of CB2 in NSCLC tissues and corresponding paracancerous tissues was examined using immunohistochemical staining assay. The expression of CB2 was silenced by siRNA interference and loss-of-function assays were performed to investigate the biological function of CB2 in the proliferation, migration, invasion, and apoptosis of NSCLC cells. The expression of related proteins was detected using western blot analysis. RESULTS: In this study, we observed that CB2 was up-regulated in NSCLC tissues and the up-regulation was correlated with tumor size and advanced NSCLC pathological grading. Moreover, compared with the control group, silencing of CB2 decreased the proliferation, migration and invasion abilities of A549 and H1299 cells, and induced apoptosis by regulation of Bcl-2/Bax axis and active Caspase3. Furthermore, CB2 knockdown inactivated the Akt/mTOR/P70S6K pathway by decreasing the level of p-Akt, p-mTOR and expression of P70S6K in A549 and H1299 cells. CONCLUSION: Our data suggested that targeting CB2 may inhibit the growth and survival of NSCLC cells, which the Akt/mTOR/P70S6K pathway may be involved in. These results confer the pro-oncogenic role of CB2 in the progression of NSCLC, thus improving our understanding of CB2 in tumor progression.
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