Korean J Thorac Cardiovasc Surg.  2001 May;34(5):377-385.

Resistance to Cisplatin Renders High Metastatic Potential in Human Non-Small Cell Lung Cancer Cell Line

• Cha DW
• Kim JG
• Sohn DS
• Cho DY
• Yang KM

Abstract

BACKGROUND: Resistance to cytotoxic drugs such as cisplatin is an important cause of treatment failure in lung cancer. The mechanisms are omplex and have yet to be clearly elucidated, but the acquisition of drug resistance possibly has resulted in poor survival. The purpose of the study is to evaluate whether the resistant tumor cells would gain more potential for metastasis. MATERIAL AND METHOD: we examined the metastatic potential of a cisplatin-reisistant cell line, H460/CIS, which was established from the human lung cancer cell line H460 by in vitro selection with gradually increased concentration of cisplatin. The parental cisplatin-sensitive cell line(H460) was used as the control and analysis on the expression of angiogenesis or growth-related factors, gelatin zymographic analysis and in vivo spontaneous metastatic experiment in nude mice were done. RESULT: Increased levels of vascular endothelial growth factor(VEGF) and basic fibroblast growth factor (bFGF) were found in H460/CIS. Gelatin zymographic analyses showed that proteinase A in the culture medium of H460/CIS was processed from latent to activated form. The in vivo experiment showed that H460/CIS cells spontaneously metastasized to the lungs but parental cells did not.
CONCLUSION
resistance to the chemotherapeutic agents may render the tumor aggressi-veness and metastatic potential. Therefore, the risk, rather than benefit, from inadvertent application of adj uvant or neoadj uvant chemotherapy to early-staged lung cancer should be considered.

Keyword

Carcinoma, non-small cell, lung; Cisplatin; Neoplasm metastasis

MeSH Terms

Animals
Carcinoma, Non-Small-Cell Lung*
Cell Line*
Cisplatin*
Drug Resistance
Drug Therapy
Fibroblast Growth Factor 2
Gelatin
Humans*
Lung
Lung Neoplasms
Mice
Mice, Nude
Neoplasm Metastasis
Parents
Treatment Failure
Cisplatin
Fibroblast Growth Factor 2
Gelatin