Shikonin promotes adriamycin‑induced apoptosis by upregulating caspase‑3 and caspase‑8 in osteosarcoma

Yang,Qing; Li,Suoyuan; Fu,Zeze; Lin,Binhui; Zhou,Zifei; Wang,Zhuoying; Hua,Yingqi; Cai,Zhengdong

doi:10.3892/mmr.2017.6729

Shikonin promotes adriamycin‑induced apoptosis by upregulating caspase‑3 and caspase‑8 in osteosarcoma

Authors:
- Qing Yang
- Suoyuan Li
- Zeze Fu
- Binhui Lin
- Zifei Zhou
- Zhuoying Wang
- Yingqi Hua
- Zhengdong Cai
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Affiliations: Department of Orthopedics, Nanjing Medical University Shanghai Tenth People's Hospital, Nanjing, Jiangsu 210029, P.R. China, Department of Orthopedics, Shanghai General Hospital, Nanjing Medical University, Shanghai 201600, P.R. China, Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 201600, P.R. China
Published online on: June 8, 2017 https://doi.org/10.3892/mmr.2017.6729
Pages: 1347-1352
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteosarcoma is the most common primary malignant bone tumor. Cancer cells employ a host of mechanisms to develop resistance to adriamycin (ADM) or other chemotherapeutic drugs. Shikonin (SK), an active constituent extracted from a Chinese medicinal herb, has been shown to cooperate with ADM in the treatment of osteosarcoma and certain other types of cancer by contributing to the response rate of chemotherapy and the side effects. The aim of the present study was to investigate the role and underlying mechanism of SK in chemotherapy for osteosarcoma. In the present study, a CCK-8 assay was performed to assess cell survival rate in vitro. Western blot analysis was performed to determine the expression levels of B‑cell lymphoma 2‑associated X protein (Bax), caspase‑3, caspase‑8, and poly (ADP‑ribose) polymerase (PARP). Flow cytometry was used to analyze cell cycle and cell death. The survival rate of cells decreased significantly in a dose‑ and time‑dependent manner when treated with a combination of SK and ADM. Western blot analysis revealed increased expression levels of Bax, caspase‑3, caspase‑8 and PARP in U2OS and MG63 cells 48 h following treatment with SK and ADM. Flow cytometric analysis showed that the combined treatment of SK and ADM significantly induced apoptosis in the osteosarcoma cells. Taken together SK cooperated with ADM to promote apoptosis, possibly by inducing caspase‑3‑ and caspase‑8‑dependent apoptosis. SK may be a potential enhancer in the treatment of drug‑resistant primary osteosarcoma.

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