STI 571 potentiates the sensitivity of non-small cell lung cancer cell line A549 to cytotoxic effects of cisplatin in vitro
10.3781/j.issn.1000-7431.2008.08.003
- Author:
Song-Wen ZHOU
1
Author Information
1. Department of Medical Oncology
- Publication Type:Journal Article
- Keywords:
Carcinoma;
Cisplatin;
Drug resistance, neoplasm;
Non-small cell lung;
Proliferation inhibition;
STI 571
- From:
Tumor
2008;28(8):646-650
- CountryChina
- Language:Chinese
-
Abstract:
Objective: This study was designed to compare the effects of STI 571 on proliferation, cell phases, and apoptosis between A549 and cisplatin-resistant A549 cells (A549/DDP) and detect the expressions of STI 571-related receptors in non-small cell lung cancer (NSCLC) tissues. Methods: A549 and cisplatin-resistant A549 cells (A549/DDP) were cultured in vitro. The cell proliferation was measured by MTT assay. Cell cycle distribution and apoptosis induced by STI 571, cisplatin and their combination were detected by flow cytometry in NSCLC cell lines. The expressions of platelet-derived growth factor receptor (PDGFRs) -α and-β and c-KIT in the non-small cell lung cancer cell lines and tissues were investigated by immunocytochemistry and immunchistochemistry, respectively. Kaplan-Meier survival curves were used to compare the correlation of PDGFR-α and-β expression with total survival of NSCLC patients. Results: STI 571 inhibited proliferation of A549/DDP cells, sensitized them to cisplatin chemotherapy, increased the cell number in G2/M and S phase, and induced apoptosis. However, STI 571 at the concentration below 10 μmol/L had no effect on the proliferation of A549 cells. Both A549 and A549/DDP cells expressed PDGFR-α and-β, but c-KIT expression was only observed in A549/DDP cells. The expression rates of PDGFR-α and-β were 65.5% and 69% in pulmonary adenocarcinoma, similar to those in squamous carcinoma (70.4% and 74.1%). Only one case of squamous carcinoma expressed c-Kit (3.7%). The PDGFR-α or β-positive patients had similar 3-year survival rates and overall survival time with the PDGFRα or β-negative patients. Conclusion: ST1 571 could suppress proliferation of A549/DDP cells, induce apoptosis and increase the sensitivity of A549/DDP to cisplatin. The levels of PDGFRα and β expression did not correlate with the prognosis of NSCLC patients.
