Ivermectin Augments the In Vitro and In Vivo Efficacy of Cisplatin in Epithelial Ovarian Cancer by Suppressing Akt/mTOR Signaling

Ivermectin: An Anthelmintic, an Insecticide, and Much More

“…Juarez et al [75] and Antoszczak et al [76] have reviewed the anticancer effects of ivermectin at high concentrations (0.1-100 μM or doses of 3-40 mg/kg) in tissue culture and in mice. The modes of action of ivermectin on different types of cancer are proposed to involve different mechanisms: (i) the multidrug-resistance transporter protein [77]; (ii) Akt/mTOR [78] and WNT-TCF pathways [79]; (iii) purinergic receptors [80]; (iv) PAK-1 [81]; (v) the cancer-related epigenetic deregulators SIN3A and SIN3B, RNA helicase; (vi) effects on mammalian tubulin polymerization and depolymerization dynamics [82]; and (vii) preferential targeting of cancer stem-cell-like populations [83]. The potential for repurposing ivermectin for cancer treatment remains to be established, as does the mechanisms of action.…”

Recycling the Purpose of Old Drugs to Treat Ovarian Cancer

“…OC patients with high expression of KPNB1 present poor survival, consequently, ivermectin represents a promising candidate for combinatory treatment in OC. Recently, an interesting study suggest that ivermectin may useful OC combinatory treatments, demonstrating that this drug significantly augmented cisplatin inhibitory effect by suppressing the phosphorylation of key molecules in Akt/mTOR signalling pathway [ 180 ]. In same study, using an OC xenograft mouse models, authors showed that ivermectin alone inhibit tumour growth and, in combination with cisplatin, completely reversed tumour growth [ 180 ].…”

“…Recently, an interesting study suggest that ivermectin may useful OC combinatory treatments, demonstrating that this drug significantly augmented cisplatin inhibitory effect by suppressing the phosphorylation of key molecules in Akt/mTOR signalling pathway [ 180 ]. In same study, using an OC xenograft mouse models, authors showed that ivermectin alone inhibit tumour growth and, in combination with cisplatin, completely reversed tumour growth [ 180 ]. Corroborating these findings, another in vivo and vitro study demonstrated that ivermectin reverse the chemoresistance in colorectal, breast, and chronic myeloid leukaemia cancer cells by inhibit epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinases (ERK)/Akt/nuclear factor kappa B (NF-κB) pathway ( Figure 1 ) [ 181 ].…”

Ivermectin, a potential anticancer drug derived from an antiparasitic drug

“…Interestingly, IVM and paclitaxel have a synergistic effect on ovarian cancer, and combined treatment in in vivo experiments almost completely inhibited tumor growth. Furthermore, according to a report by Zhang, IVM can enhance the efficacy of cisplatin to improve the treatment of epithelial ovarian cancer, and the mechanism is related to the inhibition of the Akt/mTOR pathway [ 60 ].…”

“…An experiment found that IVM could significantly enhance the inhibitory effects of erlotinib and cetuximab on lung cancer and colorectal cancer [ 50 ]. Earlier, we mentioned that IVM combined with conventional chemotherapeutic drugs such as cisplatin [ 60 ], paclitaxel [ 59 ], daunorubicin and cytarabine [ 51 ], or with targeted drugs such as dasatinib [ 53 ] and dapafenib [ 73 ] shows great potential for cancer treatment. The combination of drugs can effectively increase efficacy, reduce toxicity or delay drug resistance.…”