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Sodium cantharidate targets STAT3 and abrogates EGFR inhibitor resistance in osteosarcoma.
Aging (Albany NY) 2019; 11(15):5848-5863A

Abstract

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Overactive EGFR signaling is frequently seen in osteosarcoma cells, and represents a potential therapeutic target. However, feedback activation of STAT3 after EGFR inhibition is linked to treatment resistance, suggesting that combined EGFR/STAT3 inhibition may be needed to overcome this effect. Cantharidin and its analogues have shown strong anticancer effects, including STAT3 inhibition, in several tumor cells. Therefore, we investigated the effects of sodium cantharidate (SC), either as monotherapy and in combination with the EGFR inhibitor erlotinib, on STAT3 activation and osteosarcoma cell growth. Cell viability, migration, and apoptosis assays were performed in human MG63 and U2OS cells, and MG63 xenografts were generated in nude mice to verify the suppression of tumor growth in vivo. Additionally, western blotting and immunohistochemistry were used to verify the STAT3 and EGFR phosphorylation statuses in xenografts. We found that SC repressed cell viability and migration and induced apoptosis in vitro, while combined SC and erlotinib treatment enhanced osteosarcoma growth suppression by preventing feedback activation of STAT3. These data support further development of cantharidin-based combination therapies for metastatic and recurrent/refractory osteosarcoma.

Authors+Show Affiliations

Department of Orthopedic Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.Department of Orthopedic Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31422383

Citation

Ji, Xiang Lu, and Ming He. "Sodium Cantharidate Targets STAT3 and Abrogates EGFR Inhibitor Resistance in Osteosarcoma." Aging, vol. 11, no. 15, 2019, pp. 5848-5863.
Ji XL, He M. Sodium cantharidate targets STAT3 and abrogates EGFR inhibitor resistance in osteosarcoma. Aging (Albany NY). 2019;11(15):5848-5863.
Ji, X. L., & He, M. (2019). Sodium cantharidate targets STAT3 and abrogates EGFR inhibitor resistance in osteosarcoma. Aging, 11(15), pp. 5848-5863. doi:10.18632/aging.102193.
Ji XL, He M. Sodium Cantharidate Targets STAT3 and Abrogates EGFR Inhibitor Resistance in Osteosarcoma. Aging (Albany NY). 2019 Aug 15;11(15):5848-5863. PubMed PMID: 31422383.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sodium cantharidate targets STAT3 and abrogates EGFR inhibitor resistance in osteosarcoma. AU - Ji,Xiang Lu, AU - He,Ming, Y1 - 2019/08/15/ PY - 2019/06/18/received PY - 2019/08/10/accepted PY - 2019/8/19/entrez PY - 2019/8/20/pubmed PY - 2019/8/20/medline KW - EGFR KW - STAT3 KW - osteosarcoma KW - resistance KW - sodium cantharidate SP - 5848 EP - 5863 JF - Aging JO - Aging (Albany NY) VL - 11 IS - 15 N2 - Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Overactive EGFR signaling is frequently seen in osteosarcoma cells, and represents a potential therapeutic target. However, feedback activation of STAT3 after EGFR inhibition is linked to treatment resistance, suggesting that combined EGFR/STAT3 inhibition may be needed to overcome this effect. Cantharidin and its analogues have shown strong anticancer effects, including STAT3 inhibition, in several tumor cells. Therefore, we investigated the effects of sodium cantharidate (SC), either as monotherapy and in combination with the EGFR inhibitor erlotinib, on STAT3 activation and osteosarcoma cell growth. Cell viability, migration, and apoptosis assays were performed in human MG63 and U2OS cells, and MG63 xenografts were generated in nude mice to verify the suppression of tumor growth in vivo. Additionally, western blotting and immunohistochemistry were used to verify the STAT3 and EGFR phosphorylation statuses in xenografts. We found that SC repressed cell viability and migration and induced apoptosis in vitro, while combined SC and erlotinib treatment enhanced osteosarcoma growth suppression by preventing feedback activation of STAT3. These data support further development of cantharidin-based combination therapies for metastatic and recurrent/refractory osteosarcoma. SN - 1945-4589 UR - https://www.unboundmedicine.com/medline/citation/31422383/Sodium_cantharidate_targets_STAT3_and_abrogates_EGFR_inhibitor_resistance_in_osteosarcoma L2 - https://www.impactaging.com/full/11/5848 DB - PRIME DP - Unbound Medicine ER -
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