534P - DSC2 promotes the proliferation, metastasis and drug resistance of lung cancer by activating the PI3K/AKT pathway

Background

Lung cancer is a major health concern worldwide. It is the leading cause of cancer-related deaths among both men and women. The current study aims to investigate the role of desmocollin 2 (DSC2) protein in the proliferation, migration, drug resistance and immunotherapy of lung cancer cells. Lung cancer is a major health concern worldwide.

Methods

To examine the role of DSC2 in lung cancer cells, various assays were performed, including CCK-8 and colony formation assays to assess the impact on cell viability and colony formation, respectively. Transwell and wound-healing assays were also conducted to evaluate the impact on cell migration. The flow cytometry double staining assay was employed to detect the apoptosis rate of cells with DSC2 added with cisplatin. Western blotting analysis was used to examine the levels of cell cycle, PI3k/Akt, and apoptosis-related proteins.

Results

The results of this study revealed that DSC2 is upregulated in clinical lung cancer tissues compared to pericarcinomatous tissues and differentially expressed in lung cancer cell lines. The down-regulation of DSC2 in A549 and H358 lung cancer cells significantly reduced cell proliferation, metastasis, and motility. In addition to lung adenocarcinoma cell lines, we also examined its expression in lung squamous cell lines, such as H226. However, the overexpression of DSC2 in H23 and PC9 cell lines showed opposite effects. Western blotting showed that DSC2 could reduce the level of phosphorylated Akt (Ser 473) and p-mTOR. Thus, the study suggested that DSC2 up-regulation promotes proliferation and invasiveness through activation of the PI3K/AKT pathway. DSC2 knockdown can significantly decrease the levels of cyclinB and wee1 protein in A549 and H226. Cisplatin combined with DSC2 knockdown can enhance cell apoptosis rates.

Conclusions

These data suggest that dsc2 promotes the proliferation and migration of lung cancer cells in vitro. Also, the results suggested that dsc2 could affect the cell cycle and apoptosis of lung cells. Furthermore, knockdown of dsc2 could sensitize cisplatin in both lung adenocarcinoma and lung squamous cell lines. Thus, we suggested that dsc2 can be used as a therapeutic target for lung cancer.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Affiliated Hangzhou First People’s Hospital of Zhejiang university.

Disclosure

All authors have declared no conflicts of interest.