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Journal of Cancer Research and Clinical Oncology

Published in:

01-01-2018 | Original Article – Cancer Research

Additive naftopidil treatment synergizes docetaxel-induced apoptosis in human prostate cancer cells

Authors: Kenichiro Ishii, Izumi Matsuoka, Shinya Kajiwara, Takeshi Sasaki, Manabu Miki, Manabu Kato, Hideki Kanda, Kiminobu Arima, Taizo Shiraishi, Yoshiki Sugimura

Published in: Journal of Cancer Research and Clinical Oncology | Issue 1/2018

Abstract

Purpose

Docetaxel (DTX) is a standard chemotherapeutic drug for castration-resistant prostate cancer (CRPC), although adverse events are common. To overcome this problem, researchers have evaluated the efficacy of DTX treatment in combination with other drugs. Naftopidil is a tubulin-binding drug with fewer adverse events, implying the usefulness of this drug in clinical applications when combined with DTX. Here, we investigated the efficacy of additive naftopidil treatment in combination with DTX on prostate cancer (PCa) cells.

Methods

The effects of combination treatment with DTX plus naftopidil were analyzed using two animal models of LNCaP cells plus PrSC xenografts (sub-renal capsule grafting) and PC-3 xenografts (intratibial injection).

Results

Combination treatment with DTX plus naftopidil significantly inhibited cell growth in LNCaP cells compared with DTX alone. Analysis of the cooperativity index (CI) showed that combination treatment exhibited additive effects on DTX-induced growth inhibition in LNCaP cells. In contrast, combination treatment showed more than an additive (synergistic) effect on DTX-induced apoptosis in LNCaP and PC-3 cells. In LNCaP cells plus PrSC xenografts, combination treatment showed synergistic effects on DTX-induced apoptosis. The synergistic effects of naftopidil on DTX-induced apoptosis were also observed in PC-3 xenografts.

Conclusions

Our results demonstrated that additive naftopidil treatment in combination with DTX increased the efficacy of DTX for the treatment of LNCaP and PC-3 tumors in vivo. Thus, additive naftopidil treatment showed a synergistic effect on DTX-induced apoptosis in PCa cells in vitro and in vivo, suggesting that this treatment approach may yield improved clinical benefits compared with DTX alone.

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Title: Additive naftopidil treatment synergizes docetaxel-induced apoptosis in human prostate cancer cells
Authors: Kenichiro Ishii
Izumi Matsuoka
Shinya Kajiwara
Takeshi Sasaki
Manabu Miki
Manabu Kato
Hideki Kanda
Kiminobu Arima
Taizo Shiraishi
Yoshiki Sugimura
Publication date: 01-01-2018
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 1/2018
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-017-2536-x

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Purpose

Methods

Results

Conclusions

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