1995 Fiscal Year Final Research Report Summary

Inhibition of lung cancer cell growth by antisense oligonucleotide to tumor growth factor gene

Research Project

Project/Area Number	06671360
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Thoracic surgery
Research Institution	Dokkyo University
Principal Investigator	CHIMOTO Masayuki Dokkyo Univ.Sch.Med., Lecture, 医学部, 講師 (40191902)
Co-Investigator(Kenkyū-buntansha)	SHIMADA Koichiro Dokkyo Univ.Sch.Med., Professor, 医学部, 教授 (60009488) YASUDA Shin-ichi Dokkyo Univ.Sch.Med., Instractor, 医学部, 研究員 (60133279)
Project Period (FY)	1994 – 1995
Keywords	Lung cancer / Growth inhibition / Molecular analysis / Antisense oligonucleotide
Research Abstract	Usually the specificity of basis on cell cytotoxity for cancer chemotherapy has been dependent upon the uptake ratio of drugs to difference of originate in cell growth between tumor and normal cells. In advance tumor account of most of tumors, because getting good results by long prognosis of chemotherapy for patients was insufficient, now new drugs and therapy are expected eagerly. Then we made plan for the specific inhibition of tumor cell growth in lung cancer by oligonucleotides, founded on information of cell biology. The target gene we chose were transforming growth factor-alpha (TGF-alpha), which we considered the high expression on lung cancer, frequency of crisis, and having resistance for chemotherapy in adenocarcinoma. We produced phosphorothioate-modified antisense oligonucleotide spanning the 3-end codons of TGF-alpha mRNA.Analysis of TGF-alpha mRNA expression in cancer cell lines by RT-PCR,we observed 7 lines of lung cancer and osteosarcoma line, and especially strong expression of these gene were shown in 3 lung cancer cell lines. Antisense oligonucleotide suppressed the growth of HPC-93EP cells, which expressed TGF-alpha gene strongly, the effect was on dose dependent manner, on other hand the sense oligonucleotide had no effect. TGF-alpha antisense oligonucleo-tide decreased TGF-alpha mRNA and protein expression when analyzed by RT-PCR and flow cytometry. Thus antisense oligonucleotide to growth factor might be promising as a possible therapy for lung cancers.