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HSP70 desensitizes osteosarcoma cells to baicalein and protects cells from undergoing apoptosis
Lianghua Ding1, Shuanghua He, Xiaoliang Sun
1Department of Orthopedics, The Third Affiliated Hospital of Suzhou University, No 185 Juqian Street, Changzhou, 213003, China.
Abstract:
Baicalein is a new drug that has shown promising anti-cancer effects against a broad spectrum of tumors. However, the potential effect on osteosarcoma cells and the mechanisms involved are still largely unknown. Resistance to chemotherapy remains a major obstacle in cancer therapy. Therefore, the aim of the present study was to investigate the anti-tumor effect of baicalein on human osteosarcoma cancer cells and the molecular mechanism involved, as well as identify possible mechanisms of drug resistance. Our results revealed that baicalein-induced apoptosis in osteosarcoma cells was via a mitochondrial pathway involving both caspase-dependent and independent mechanisms. Notably, baicalein treatment upregulated the expression of HSP70, which partially prevented human osteosarcoma cells from undergoing apoptosis. Moreover, it was revealed that HSP70 expression decreased the sensitivity of osteosarcoma cells to baicalein via activation of PI3K/AKT and MAPK/ERK pathways. These results suggest that targeting HSP70-mediated drug resistance, in combination with chemotherapy drugs, may provide novel therapeutic opportunities.
Insights
Baicalein induces apoptosis in osteosarcoma cells through a mitochondrial pathway. Targeting heat shock protein 70 (HSP70) may overcome drug resistance in cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Baicalein demonstrates broad-spectrum anti-cancer properties.
- The effects of baicalein on osteosarcoma and its resistance mechanisms are not well understood.
- Chemotherapy resistance is a significant challenge in treating osteosarcoma.
Purpose of the Study:
- To investigate the anti-tumor effects of baicalein on human osteosarcoma cells.
- To elucidate the molecular mechanisms underlying baicalein's action.
- To identify potential mechanisms of drug resistance.
Main Methods:
- Cell viability assays to assess baicalein's effect.
- Apoptosis assays to detect programmed cell death.
- Western blotting to analyze protein expression (HSP70, caspases, PI3K/AKT, MAPK/ERK pathways).
Main Results:
- Baicalein induced apoptosis in osteosarcoma cells via mitochondrial pathways (caspase-dependent and independent).
- Baicalein upregulated heat shock protein 70 (HSP70) expression, conferring partial resistance to apoptosis.
- HSP70 activation of PI3K/AKT and MAPK/ERK pathways reduced osteosarcoma cell sensitivity to baicalein.
Conclusions:
- Baicalein exhibits anti-osteosarcoma activity by inducing apoptosis.
- HSP70 plays a crucial role in baicalein resistance through PI3K/AKT and MAPK/ERK signaling.
- Targeting HSP70 in combination with baicalein could be a promising therapeutic strategy for osteosarcoma.
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