Low-dose Docetaxel Enhanced the Anticancer Effect of Temsirolimus by Overcoming Autophagy in Prostate Cancer Cells.

Authors :: Inamura SO
Ito H
Taga M
Tsuchiyama K
Hoshino H
Kobayashi M
Yokoyama O
Source :: Anticancer research [Anticancer Res] 2019 Oct; Vol. 39 (10), pp. 5417-5425.
Publication Year :: 2019
Abstract: Background/aim: Chemotherapy with docetaxel (DTX) is used for castration-resistant prostate cancer (CRPC), but it is inadequate.<br />Materials and Methods: We evaluated the effect of the combination treatment DTX and the mTOR inhibitor temsirolimus (TEM) in the PC3 prostate cancer cell line, by focusing on the induction of autophagy and apoptosis.<br />Results: TEM induced autophagy but not apoptosis even at a high dose, whereas DTX induced apoptosis. The combination of low-dose DTX and TEM caused a 34% suppression in cell proliferation compared to monotherapy with a higher dose of DTX. The induction of apoptosis was increased by their combination. The combination with DTX overcame the induction of autophagy by TEM. The combination treatment suppressed tumor growth 72% less than the control group after 14 days of treatment in vivo.<br />Conclusion: The combination of TEM and DTX induced apoptosis by overcoming autophagy and enhanced the anticancer effect compared to monotherapy.<br /> (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Subjects :: Animals
Apoptosis drug effects
Cell Line, Tumor
Cell Proliferation drug effects
Combined Modality Therapy methods
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
PC-3 Cells
Protein Kinase Inhibitors administration & dosage
Sirolimus administration & dosage
Antineoplastic Agents administration & dosage
Autophagy drug effects
Docetaxel administration & dosage
Prostate drug effects
Prostatic Neoplasms drug therapy
Sirolimus analogs & derivatives

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