title: Utilization of arsenic trioxide as a treatment of cisplatin-resistant non-small cell lung cancer PC-9/CDDP and PC-14/CDDP cells.
abstract: Cisplatin is a commonly used drug in combination chemotherapy. However, various malignant tumors frequently acquire resistance to cisplatin. Arsenic trioxide (ATO) has been approved as a chemotherapeutic drug for the treatment of acute promyelocytic leukemia, and the combination of ATO and cisplatin has been revealed to demonstrate synergistic effects in ovarian and small cell lung cancer cells. Thus, it was hypothesized that ATO may also be active against cisplatin-resistant non-small cell lung cancer (NSCLC) PC-9/CDDP and PC-14/CDDP cells. The present study also evaluated the effects of ATO on the cisplatin-sensitive NSCLC PC-9 and PC-14 cell lines. Notably, ATO demonstrated a markedly decreased IC50in the cisplatin-resistant PC-9/CDDP and PC-14/CDDP cells compared with the IC50in the cisplatin-sensitive parental PC-9 and PC-14 cells. Additionally, it was found that arsenite accumulation in the PC-9 cell line was affected through the downregulation of GS-X pump systems. Although it is likely that cisplatin resistance in PC-9 cells does not depend on the GS-X pump systems, ATO was effective against cisplatin-resistant NSCLC PC-9/CDDP and PC-14/CDDP cells in combination chemotherapy.
authors.affiliation: Department of Analytical Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Analytical Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ishibashi
authors.affiliation: Department of Analytical Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yumoto
authors.affiliation: Department of Genome Biology, Kinki University School of Medicine, Osaka-sayama, Osaka 589-8511, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
authors.affiliation: Department of Analytical Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ogasawara
keywords: adenosine triphosphate-binding cassette subfamily C transporter; arsenic trioxide; cisplatin resistance; glutathione