title: Role of gap junction intercellular communication in testicular leydig cell apoptosis induced by oxaliplatin via the mitochondrial pathway.
abstract: Platinum agents are widely used in the chemotherapy of testicular cancer. However, adverse reactions and resistance to such agents have limited their application in antineoplastic treatment. The aim of the present study was to determine the role of gap junction intercellular communication (GJIC) composed of Cx43 on oxaliplatin‑induced survival/apoptosis in mouse leydig normal and cancer cells using MTT, Annexin V/PI double staining assays and western blot analysis. The results showed that GJIC exerted opposite effects on the mouse leydig cancer (I-10) and normal (TM3) cell apoptosis induced by oxaliplatin. In leydig cancer cells, survival of cells exposed to oxaliplatin was substantially reduced when gap junctions formed as compared to no gap junctions. Pharmacological inhibition of gap junctions by oleamide and 18-α-glycyrrhetinic acid resulted in enhanced survival/decreased apoptosis while enhancement of gap junctions by retinoic acid led to decreased survival/increased apoptosis. These effects occurred only in high‑density cultures (gap junction formed), while the pharmacological modulations had no effects when there was no opportunity for gap junction formation. Notably, GJIC played an opposite (protective) role in normal leydig cells survival/apoptosis following exposure to oxaliplatin. Furthermore, this converse oxaliplatin‑inducing apoptosis exerted through the functional gap junction was correlated with the mitochondrial pathway‑related protein Bcl-2/Bax and caspase‑3/9. These results suggested that in testicular leydig normal/cancer cells, GJIC plays an opposite role in oxaliplatin‑induced apoptosis via the mitochondrial pathway.
authors.affiliation: Faculty of Pharmacy, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Xuhui
authors.initials: X
authors.lastname: Tong
authors.affiliation: Faculty of Pharmacy, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Han
authors.affiliation: Faculty of Pharmacy, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Yu
authors.affiliation: Faculty of Pharmacy, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Yu
authors.affiliation: Faculty of Pharmacy, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Faculty of Pharmacy, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ji
authors.affiliation: Faculty of Pharmacy, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Shuying
authors.initials: S
authors.lastname: Dong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002450:Cell Communication; D045744:Cell Line, Tumor; D002470:Cell Survival; D017629:Gap Junctions / Q000378:metabolism*; D007985:Leydig Cells / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin