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

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.

• Authors: Kenichiro Ishii, Izumi Matsuoka, Shinya Kajiwara, Takeshi Sasaki, Manabu Miki, Manabu Kato, Hideki Kanda, Kiminobu Arima, Taizo Shiraishi, Yoshiki Sugimura
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 144 Issue 1 Pg. 89-98 (Jan 2018) ISSN: 1432-1335 [Electronic] Germany
• PMID: 29098395 (Publication Type: Journal Article)

Chemical References

• Naphthalenes
• Piperazines
• Taxoids
• Docetaxel
• naftopidil

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Apoptosis (drug effects)
• Cell Growth Processes (drug effects)
• Cell Line, Tumor
• Docetaxel
• Drug Synergism
• Humans
• Male
• Mice
• Mice, Nude
• Naphthalenes (administration & dosage, pharmacology)
• Piperazines (administration & dosage, pharmacology)
• Prostatic Neoplasms (drug therapy, pathology)
• Prostatic Neoplasms, Castration-Resistant (drug therapy, pathology)
• Random Allocation
• Taxoids (administration & dosage, pharmacology)
• Xenograft Model Antitumor Assays