CAVIN2 is Frequently Silenced by CpG Methylation and Sensitizes Lung Cancer Cells to Paclitaxel and 5-FU

Abstract

Aim: To explore the biological functions and clinical significance of CAVIN2 in lung cancer. Materials & methods: Methylation-specific PCR was used to measure promoter methylation of CAVIN2. The function of CAVIN2 was tested by Cell Counting Kit-8, colony formation, Transwell, flow cytometric analysis, acridine orange/ethidium bromide, chemosensitivity assay and xenograft assay. Results: CAVIN2 is significantly downregulated by promoter methylation in lung cancer. CAVIN2 overexpression inhibits lung cancer cell migration and invasion. Furthermore, ectopic expression of CAVIN2 inhibits cell proliferation in vivo and in vitro by inducing G2/M cell cycle arrest, which sensitizes the chemosensitivity of lung cancer cells to paclitaxel and 5-fluorouracil, but not cisplatin. Conclusion: CAVIN2 is a tumor suppressor in non-small-cell lung cancer and can sensitize lung cancer cells to paclitaxel and 5-fluorouracil.

Keywords::

• CAVIN2
• cell cycle
• CpG methylation
• non-small-cell lung cancer
• paclitaxel

Acknowledgments

We would like to thank the staff of the Department of Respiratory and Critical Care Medicine and the Key Laboratory of Molecular Oncology and Epigenetics for their help in sample collection and technical assistance.

Financial & competing interest disclosure

This work was supported by the National Natural Science Foundation of China (grant number 81872380), the Natural Science Foundation of Chongqing (grant number 2016ZDXM006), Chongqing Science and Technology Commission Social Work and People’s Livelihood Security Science and Technology Innovation Project (grant number cstc2017shmsA130044). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval by the Animal Ethics Committee of the Experimental Animal Center of the Chongqing Medical University, Chongqing, China. All protocols concerning the use of patient samples in this study were approved by the Institutional Ethics Committees of the First Affiliated Hospital of Chongqing Medical University (2019-326#).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (grant number 81872380), the Natural Science Foundation of Chongqing (grant number 2016ZDXM006), Chongqing Science and Technology Commission Social Work and People’s Livelihood Security Science and Technology Innovation Project (grant number cstc2017shmsA130044). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.