Combination of NDRG2 overexpression, X-ray radiation and docetaxel enhances apoptosis and inhibits invasiveness properties of LNCaP cells

Abstract

ObjectiveN-myc downstream regulated gene 2 (NDRG2) is identified as a promising candidate tumor suppressor in several human malignancies including prostate cancer (PCa). Here, we investigated the effect of combined NDRG2 overexpression, x-ray radiation (RTX), and docetaxel (DTX) against viability and invasiveness properties of LNCaP cells. Material and methodsA plasmid harboring NDRG2 gene under transcriptional control of prostate-specific enhancing sequence regulatory element was constructed to overexpress NDRG2 in PCa cell lines. The effects of NDRG2 overexpression in combination with RTX and DTX on viability, proliferation, and apoptosis of LNCaP cells were evaluated using MTT, colony formation, and annexin V flowcytometirc assays. Migration and invasion of NDRG2-overexpressed cells as well as expression of matrix metalloproteinses-2 (MMP2) and -9 (MMP9) were also assessed using transwell chamber assay and real-time PCR. ResultsThe results of fluorescence microscopy and real-time PCR showed a high and specific overexpression of NDRG2 in LNCaP cells. Overexpression of NDRG2 significantly reduced cell viability and increased apoptosis of LNCaP cell. Migration, invasion, as well as the expression of MMP2 and MMP9, was decreased following NDRG2 overexpression. Combination of NDRG2 overexpression with RTX and DTX decreased the viability, invasion, and migration of LNCaP cells synergistically. ConclusionThese results indicate that a combination of NDRG2 overexpression with chemotherapy and radiotherapy can be considered for effective treatment of PCa.