Fig. 3
From: Various pathways of zoledronic acid against osteoclasts and bone cancer metastasis: a brief review
ZA induces caspase-dependent apoptosis, reverts chemoresistance and stimulats immune response in cancer cells through Ras/Erk1/2 pathway. ZA inhibits Ras, blocks the Ras-dependent Erk 1/2 and Akt pathways, and then reduces the phosphorylation of both Bcl-2 and Bad, activates the caspase-dependent apoptosis pathway to kill cancer cells. In addition, ZA also reduces the activity of hypoxia inducible factor-1 alpha (HIF-1α) through interrupting Ras/Erk1/2, and then suppresses the production of ATP, and decreases the drug efflux transporter P-glycoprotein (P-gp) to induce immunogenic cell death and reverses the tumor-induced immunosuppression. In addition, ZA also inhibits the signal transducer and activator of transcription-3 (STAT3)/ indoleamine 2,3 dioxygenase (IDO) axis via Ras/Erk1/2 pathway