Highly Halaven-resistant KBV20C Cancer Cells Can Be Sensitized by Co-treatment with Fluphenazine.

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 G2 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.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Cheon JH,Lee BM,Kim HS,Yoon S

doi

10.21873/anticanres.11172

subject

Has Abstract

pub_date

2016-11-01 00:00:00

pages

5867-5874

issue

11

eissn

0250-7005

issn

1791-7530

pii

36/11/5867

journal_volume

36

pub_type

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