Combination treatment with paclitaxel and doxorubicin inhibits growth of human esophageal squamous cancer cells by inactivation of Akt

Lee,Hwan  Hee; Ye,Shuai; Li,Xiu  Juan; Lee,Kwang  Bok; Park,Man  Hee; Kim,Soo  Mi

doi:10.3892/or.2013.2851

Combination treatment with paclitaxel and doxorubicin inhibits growth of human esophageal squamous cancer cells by inactivation of Akt

Authors:
- Hwan Hee Lee
- Shuai Ye
- Xiu Juan Li
- Kwang Bok Lee
- Man Hee Park
- Soo Mi Kim
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Affiliations: Department of Physiology, Institute for Medical Sciences, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, Republic of Korea, Department of Orthopedic Surgery, Institute for Medical Sciences, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, Republic of Korea, Catholic University of Pusan, Busan, Republic of Korea
Published online on: November 14, 2013 https://doi.org/10.3892/or.2013.2851
Pages: 183-188

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Abstract

Despite the fact that paclitaxel and doxorubicin are widely used as chemotherapy agents against several types of cancer, their combined effects on esophageal squamous cell carcinoma (ESCC) have never been fully elucidated. The present study was designed to investigate the biological effects of paclitaxel and doxorubicin in ESCC cells. Combination treatment with paclitaxel and doxorubicin significantly inhibited the proliferation of TE-12 cells in a dose-and time-dependent manner compared to treatment with paclitaxel or doxorubicin alone. FACS analysis showed that the percentage of cells in the G2/M phase was significantly increased at 12 h after treatment with the combination. Increased p-cdc2, p-Wee1 and p53 protein levels were observed, while Akt activation was suppressed by combination treatment with paclitaxel and doxorubicin. In addition, treatment with paclitaxel plus doxorubicin significantly increased apoptosis as indicated by increased cleaved poly(ADP-ribose) polymerase and cleaved caspase-7 and -9 levels. These results suggest that combination treatment with paclitaxel and doxorubicin induced G2/M cell cycle arrest and apoptosis in human ESCC cells by suppressing Akt activity. These findings highlight the potent apoptotic effect of combination therapy with paclitaxel and doxorubicin in ESCC cells and the potential clinical benefits of these two drugs in esophageal cancer.

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