The oncogenic role of CB2 in the progression of non-small-cell lung cancer

Biomed Pharmacother. 2019 Sep:117:109080. doi: 10.1016/j.biopha.2019.109080. Epub 2019 Jun 5.


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.

Keywords: Akt/mTOR/P70S6K pathway; CB2; NSCLC; Tumor progression.

MeSH terms

  • A549 Cells
  • Apoptosis / genetics
  • Carcinogenesis / genetics*
  • Carcinogenesis / pathology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Oncogenes / genetics*
  • Receptor, Cannabinoid, CB2 / genetics*
  • Signal Transduction / genetics


  • CNR2 protein, human
  • Receptor, Cannabinoid, CB2