Highly Halaven-resistant KBV20C Cancer Cells Can Be Sensitized by Co-treatment with Fluphenazine
- Authors
- Cheon, J.H.[Cheon, J.H.]; Lee, B.M.[Lee, B.M.]; Kim, H.S.[Kim, H.S.]; Yoon, S.[Yoon, S.]
- Issue Date
- Nov-2016
- Publisher
- INT INST ANTICANCER RESEARCH
- Keywords
- Drug-resistance; Fluphenazine; Halaven; Mefloquine; P-gp; Thioridazine
- Citation
- ANTICANCER RESEARCH, v.36, no.11, pp.5867 - 5874
- Indexed
- SCIE
SCOPUS
- Journal Title
- ANTICANCER RESEARCH
- Volume
- 36
- Number
- 11
- Start Page
- 5867
- End Page
- 5874
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/34538
- DOI
- 10.21873/anticanres.11172
- ISSN
- 0250-7005
- Abstract
- Aim: To identify conditions that induce an increase in the sensitivity of highly Halaven (HAL)-resistant cancer cells compared to sensitive cells. Materials and Methods: We observed that drug-resistant KBV20C cells are highly resistant to HAL compared to other antimitotic drugs. The concentration required to treat KBV20C cells was almost 500-fold higher than that used to treat sensitive parent KB cells. In order to increase sensitization, HAL-treated KBV20C cells were co-treated with the repositioned drug, fluphenazine (FLU). Results: HAL and FLU co-treatment inhibited the growth and increased apoptosis via G(2) arrest in HAL-treated KBV20C cancer cells. Sensitization by HAL-FLU affected retinoblastoma protein (pRB), pHistone H3 and pH2AX protein levels. FLU could also inhibit p-glycoprotein (P-gp) activity in HA-resistant KBV20C cells. These observations suggest that the mechanisms underlying FLU-HAL sensitization in resistant KBV20C cells involve both apoptosis and P-gp inhibition. Furthermore, both thioridazine (THIO) and mefloquine (MEF), but not azathioprine (AZA), sensitized HAL-treated KBV20C cells. Conclusion: These findings provide important information regarding the sensitization of HAL-resistant cells and indicate that FLU, THIO and MEF may have similar sensitization effects in highly HAL-resistant cells.
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Collections - Pharmacy > Department of Pharmacy > 1. Journal Articles
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