In Vitro Analysis of the Relationships Between Metallothionein Expression and Cisplatin Sensitivity of Non-small Cellular Lung Cancer Cells

Background: Cisplatin-based therapy is a pivotal type of chemotherapy for non-small cell lung cancer (NSCLC) and chemoresistance to cisplatin represents one of the most significant barriers to improving long-term clinical outcomes. Materials and Methods: The present study aimed at examining metallothionein (MT) expression in six NSCLC cell lines as well as examining effects of exposure to cisplatin on MT expression in the most cisplatin-resistant (97/97) and the cisplatin-sensitive (DV90) cell lines. Results: The most cisplatin-resistant NSCLC cell line [97197; (IC50)=4.659 mu M] exposed to the highest concentration of cisplatin (10 mu M) exhibited decreased nuclear MT expression (MTn=6) compared to cells cultured in medium with a lower concentration of cisplatin (0, 1 and 5 mu M) (MTn=12). A higher cytoplasmic metallothionein expression (MTc=6) was found in the 97197 cell line exposed to the highest concentration of cisplatin (10 mu M), compared to cells cultured in the medium with lower concentrations of cisplatin (0, 1 and 5 mu M) (MTc=3). The most cisplatin-sensitive NSCLC cell line (DV90; IC50=0.184 mu M) was characterized by a significant decrease of both nuclear and cytoplasmic MT expression with increasing cisplatin concentrations (5 vs. 10 mu M). Conclusion: Nuclear and cytoplasmic expression of MT has no significant impact on the development of cisplatichemoresistance in NSCLC cell lines. The present study suggests that cisplatin resistance in NSCLC is metallothionein-independent.