Regulation of chemosensitivity and migration by clusterin in non-small cell lung cancer cells

Purpose: In terms of drug resistance, cancer cells usually benefit from high clusterin (CLU) expression on chemotherapy. In contrast, CLU expression has been found to be a favorable prognostic factor in lung cancer patients. The aims of this study are to determine the association between CLU expression and chemotherapeutic sensitivity and the potential role of CLU in migration in human non-small-cell lung cancer (NSCLC) cell lines.

Methods: The levels of clusterin in NSCLC cell lines were altered by short hairpin RNA interference (shRNAi) and overexpression on chemosensitivity assay. Migratory ability of these cell lines was also investigated.

Results: H1355 cells with the highest level of CLU demonstrated the lowest sensitivities to Adriamycin (ADR), docetaxel (DOC), and gemcitabine (GEM) treatment. Inhibition of CLU expression in H1355 cells resulted in higher chemosensitivities. When CLU was stably overexpressed in A549 and H1299 cells, only the chemosensitivity to ADR was reduced. The migratory ability of CLU-overexpressing cells significantly decreased. Moreover, MMP2 transcription was inhibited in CLU-overexpressing H1299 cells. These results indicated lower metastatic potential for cancer cells with high CLU level.

Conclusion: Lung cancer cells with high level of CLU have reduced chemosensitivity. High level of CLU may result in migratory inhibition and thus favorable prognosis in lung cancer.