Shikonin promotes adriamycin‑induced apoptosis by upregulating caspase‑3 and caspase‑8 in osteosarcoma
Qing Yang1, Suoyuan Li2, Zeze Fu3
1Department of Orthopedics, Nanjing Medical University Shanghai Tenth People's Hospital, Nanjing, Jiangsu 210029, P.R. China.
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.
Insights
Shikonin (SK) enhances adriamycin (ADM) chemotherapy for drug-resistant osteosarcoma by promoting apoptosis. This combination therapy increases the expression of apoptosis-related proteins, offering a potential new treatment strategy.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Osteosarcoma is the most common primary bone malignancy.
- Cancer cells develop resistance to chemotherapy drugs like adriamycin (ADM).
- Shikonin (SK), derived from Chinese medicinal herbs, shows potential in cancer treatment.
Purpose of the Study:
- To investigate the role and mechanism of SK in osteosarcoma chemotherapy.
- To evaluate SK's effect on ADM resistance in osteosarcoma cells.
Main Methods:
- Cell viability assessed using CCK-8 assay.
- Protein expression of Bax, caspase-3, caspase-8, and PARP analyzed by Western blot.
- Cell cycle and apoptosis analyzed via flow cytometry.
Main Results:
- Combined SK and ADM treatment significantly reduced osteosarcoma cell survival in a dose- and time-dependent manner.
- Increased expression of Bax, caspase-3, caspase-8, and PARP observed post-treatment.
- Significant induction of apoptosis in osteosarcoma cells by the combined SK and ADM therapy.
Conclusions:
- SK cooperates with ADM to enhance chemotherapy efficacy in osteosarcoma.
- The mechanism involves the induction of caspase-3- and caspase-8-dependent apoptosis.
- SK shows promise as an enhancer for treating drug-resistant osteosarcoma.
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