Study on augementation of chemotherapeutic effect by anticancer drugs in human lung cancers: Analysis of drug resistance in cancer cells.

Research Project

Project/Area Number	60570650
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Thoracic surgery
Research Institution	Dokkyo University, School of Medicine (C)
Principal Investigator	SHIMADA Koichiro Associated Professor, 医学部, 助教授 (60009488)
Co-Investigator(Kenkyū-buntansha)	YASUDA Shin-ichi Researcher of Medical Science, 医学部, 研究員 (60133279)
Project Period (FY)	1985 – 1986
Project Status	Completed (Fiscal Year 1986)
Budget Amount *help	¥1,900,000 (Direct Cost: ¥1,900,000) Fiscal Year 1986: ¥300,000 (Direct Cost: ¥300,000) Fiscal Year 1985: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywords	resistance of anticancer drug / lung cancer / metallothionein / cisplatin / trecemetal
Research Abstract	It is known that non efficacy of anti cancer drugs during treatment of the malignancy is due to the resistant mechanism in cancer cell itselves, is designed to analyze this resistant mechanism focusing upon the resistant protein metallothioneim(MT). The resistant mechanism was analyzed by means of cultured human adenocarcinoma cells of the lung. This cancer cells were treated with cis-platinum(Cys). Aliving cells cultured with Cys were observed by phase contrast microscope, scanning electro microscope (SEM), fluororescence microscope and flow cytemtry(FCM). MT in cell extract and cultured supernate was eluated by Sephadex G-75 column. Tese cells were divided to died cells and rested cells(RC). The RC re-growthed by added EGF, fibronectin and insulin as growth factors and consisted of different kind of cell groups. Nemely one has large size and another has long process. By FVM, the RC were grossly largeer than orignal cells(OC) and have different stracture both in inside and cell surface. SEM showed microviel in RC become shorter and small bleb like process in OC was lost. Doubling time was 48 h in RC and 71 h inOC. As cell marker, CEA was decreased, keratin increased and HLA not change in RC by observation with immunofluorecence tests, Sephadex G-75 profiles showed MT in RC extract and cultured supernate. In conclusion, the resistant mechanism of RC was regulated by the resistant protein,MT.