Molecular mechanism of chemoresistance to cisplatin in ovarian cancer cell lines.
It is important to clarify the mechanism of resistance to cisplatin for the treatment of solid tumors. We have examined the expression of apoptosis-related proteins, Bax and Bcl-2, in ovarian cancer cells. We used the cell line 2008 and its cisplatin resistant subclone 2008 C-13. The percentage of 2008 cells showing apoptosis was significantly higher following cisplatin treatment as compared to untreated controls. 2008 C-13 cells showing apoptosis did not differ between the cisplatin-treated group and the untreated group. The expression of mRNA and protein of Bax in the two cell lines were not altered by treatment with cisplatin. Although the expression of mRNA and protein of Bcl-2 decreased in 2008 cells after treatment with cisplatin, the expression of Bcl-2 remained unchanged in 2008 C-13 cells. Our results indicate that the down-regulation of Bcl-2 plays an important role in the mechanisms of tumor resistance to anticancer drugs.
Murata
Toshihiro
T
Departments of Gastroenterological Surgery, Transplant, and Surgical Oncology, Okayama University, Okayama 700-8558, Japan.
Haisa
Minoru
M
Uetsuka
Hirokazu
H
Nobuhisa
Tetuji
T
Ookawa
Takaomi
T
Tabuchi
Yoko
Y
Shirakawa
Yasuaki
Y
Yamatsuji
Tomoki
T
Matsuoka
Junji
J
Nishiyama
Masahiko
M
Tanaka
Noriaki
N
Naomoto
Yoshio
Y
D017209:Apoptosis / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D019254:Genes, bcl-2 / Q000502:physiology*; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D002945:Cisplatin