title: Chemotherapy agents-induced immunoresistance in lung cancer cells could be reversed by trop-2 inhibition in vitro and in vivo by interaction with MAPK signaling pathway.
abstract: Chemotherapy has been widely used in cancer treatment, but the prognosis of the cancer patients following chemotherapy has not been substantially improved. Alternative strategies such as immunotherapy and their combinations with chemotherapy are now being considered; however, the effects of chemotherapy on the immune responses of cancer cells are not fully understood. In the present studies, we reveal a potential link between chemotherapy and cancer immunoresistance, we first examined the effects of chemopreventive agent DDP on the expression of a cell surface glycopreotein Trop-2 in lung cancer cells, and found that DDP not only induce Trop-2 surface expression in human lung cancer cells, but also induce T-cell apoptosis effectively. In order to investigate the relationship between DDP-induced Trop-2 expression and T-cell apoptosis, we stably transfected A549 and PC14 lung cancer cells with Trop-2 shRNA, the DDP-induced Trop-2 surface expression was effectively decreased in stably transfected cell lines, but chemotherapeutic reagent-induced cell proliferation inhibition and apoptosis were increased through inhibition of the MAPK signaling pathway. In vivo animal experiments showed that Trop-2 knockdown tumors displayed a slower growth rate than the control xenografts. Importantly, DDP treatment exhibited a strong antitumor activity in the mice with Trop-2 knockdown tumors, but only a marginal effect in the control group. Taken together, our data show that DDP resistance in lung cancer cells could be induced through increased surface expression of Trop-2, which at least partially by interfering with MAPK pathway. These results provide novel insight into the function of Trop-2 and encourage the design and testing of approaches targeting this protein and its partners.
authors.affiliation: Department of Clinical Diagnosis; Tangdu Hospital; Fourth Military Medical University; Xi'an, PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Clinical Diagnosis; Tangdu Hospital; Fourth Military Medical University; Xi'an, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Long
authors.affiliation: Department of Clinical Diagnosis; Tangdu Hospital; Fourth Military Medical University; Xi'an, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Dong
authors.affiliation: Department of Clinical Diagnosis; Tangdu Hospital; Fourth Military Medical University; Xi'an, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Lin
authors.affiliation: Department of Clinical Diagnosis; Tangdu Hospital; Fourth Military Medical University; Xi'an, PR China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Weng
authors.affiliation: Department of Clinical Diagnosis; Tangdu Hospital; Fourth Military Medical University; Xi'an, PR China.
authors.forename: Yongri
authors.initials: Y
authors.lastname: Ouyang
authors.affiliation: Department of Clinical Diagnosis; Tangdu Hospital; Fourth Military Medical University; Xi'an, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Clinical Diagnosis; Tangdu Hospital; Fourth Military Medical University; Xi'an, PR China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Clinical Diagnosis; Tangdu Hospital; Fourth Military Medical University; Xi'an, PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Clinical Diagnosis; Tangdu Hospital; Fourth Military Medical University; Xi'an, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: He
authors.affiliation: Department of Clinical Diagnosis; Tangdu Hospital; Fourth Military Medical University; Xi'an, PR China.
authors.forename: Hui-Zhong
authors.initials: HZ
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D020935:MAP Kinase Signaling System; D051379:Mice; D008875:Middle Aged
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; C499380:TACSTD2 protein, human; D002945:Cisplatin
keywords: DDP; MAPK; Trop-2; immunoresistance; lung cancer
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