Gemcitabine and Rapamycin Exhibit Additive Effect against Osteosarcoma by Targeting Autophagy and Apoptosis

Area of Science:

• Oncology
• Pharmacology
• Cancer Biology

Background:

• Prognosis for sarcoma patients, including osteosarcoma (OS), has stagnated over the last decade.
• Chemoresistant OS lacks effective therapeutic options, necessitating novel treatment strategies.

Purpose of the Study:

• To investigate the potential of combining gemcitabine (Gem) with rapamycin (Rapa) to enhance anti-tumor effects in osteosarcoma.
• To evaluate the efficacy and safety of this combination therapy in preclinical models of OS.

Main Methods:

• In vitro studies assessed the effects of Gem and Rapa on OS cell viability, invasion, migration, and VEGF production.
• In vivo studies utilized allograft and xenograft murine models to evaluate tumor growth, angiogenesis, metastasis, and survival following combination therapy.
• Mechanistic studies examined Gem-induced apoptosis and Rapa-induced autophagy.

Main Results:

• Gem demonstrated dose-dependent cytotoxicity against OS cells with minimal impact on osteoblasts.
• The combination of Gem and Rapa significantly reduced OS cell viability, invasion, migration, and VEGF production in vitro.
• In vivo, the combination therapy suppressed tumor growth, angiogenesis, and lung metastasis, prolonging survival with minimal adverse effects.

Conclusions:

• Gemcitabine combined with rapamycin represents a novel and promising therapeutic strategy for chemoresistant osteosarcoma.
• The combination therapy induces apoptosis (Gem) and autophagy (Rapa), contributing to its enhanced anti-tumor efficacy.
• This approach warrants further investigation for clinical application in osteosarcoma treatment.