title: Metformin Enhances the Therapy Effects of Anti-IGF-1R mAb Figitumumab to NSCLC.
abstract: The insulin-like growth factor (IGF) signaling system plays a critical role in tumorigenesis, highlighting the potential of targeting IGF-1R as an anti-cancer therapy. Although multiple anti-IGF-1R monoclonal antibody (mAb) drugs have been developed, challenges remain in the validation of the therapeutic effects and understanding the molecular mechanism of these mAbs. Herein, we conducted a study to validate the effect of Figitumumab (CP), an anti-IGF-1R mAb, in a panel of non-small cell lung cancer (NSCLC) cell lines. We found all tested cell lines were sensitive to CP, and CP could block IGF-1R and the downstream PI3K/AKT pathway activation. Unexpectedly, we found CP could activate ERK signaling pathway in IGF-1R kinase independent manner, which we further verified was mainly mediated by β-arrestin2. We also investigated the anti-tumor effect of metformin alone as well as its combination with CP to target NSCLC. Metformin could target IGF-1R signaling pathway by attenuating PI3K/AKT and MEK/ERK signaling pathways and down-regulating IGF-1R. Finally, we found that combining metformin with CP could further induce IGF-1R down-regulation and was more effective to target NSCLC cells. Our data suggests the combining of metformin with CP has additive therapeutic value against NSCLC.
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, P.R. China.|Department of Chemotherapy, Cancer Center, Qilu Hospital of Shandong University, Shandong University, Jinan, P.R. China.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Dong
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Qu
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, P.R. China.
authors.forename: Hongchang
authors.initials: H
authors.lastname: Shen
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, P.R. China.
authors.forename: Linhai
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, P.R. China.|Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, P.R. China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Du
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008687:Metformin / Q000008:administration & dosage*; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D000071557:beta-Arrestins / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000071557:beta-Arrestins; D008687:Metformin; D017526:Receptor, IGF Type 1; C525021:figitumumab