title: Roles of ERα and ERβ in estrogen-induced DDP chemoresistance in non-small cell lung cancer.
abstract: The role of estrogen in inducing chemoresistance is not yet fully understood. The objective of this study was to observe the relationship between estrogen levels and cellular response to chemotherapeutic drugs in non-small cell lung cancer (NSCLC) and to reveal the potential mechanisms involved. Cell viability was analyzed after pre-treating NSCLC cells with different levels of estrogen (E2), followed by treatment with an anti-tumor drug for 48 h. The roles of various estrogen receptors (ERs) were examined in vitro by blocking the activity of each ER individually. The ER pathway was further confirmed in NSCLC tissues. It was found that 10-1000 nM E2 resulted in a decreased cellular response to DDP in H1650 cells compared to the use of cisplatin alone (P < 0.05). However, this result was not demonstrated in H1299 cells, which lack p53. Both ERa and ERb were associated with E2-induced cisplatin chemoresistance, though they had opposite functions. p53 expression did not correlate with the expression of ERa or ERb individually. However, a statistically significant correlation between p53 expression and ERa to ERb mRNA ratio was observed (P < 0.001, R = -0.676). These findings suggest that E2-induced DDP chemoresistance depends on the balance between ERa and ERb expression and the p53 pathway.
authors.affiliation: Department of Radiology, The First Affiliated Hospital, Xi'an Jiao Tong University, Xi'an, China.
authors.forename: N
authors.initials: N
authors.lastname: Yu
authors.affiliation: Department of Internal Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Dou
authors.affiliation: Department of Radiology, The First Affiliated Hospital, Xi'an Jiao Tong University, Xi'an, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Radiology, The First Affiliated Hospital, Xi'an Jiao Tong University, Xi'an, China.
authors.forename: L
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Respiratory Medicine, The Ninth Hospital of Xi'an, Xi'an, China.
authors.forename: X
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Radiology, The First Affiliated Hospital, Xi'an Jiao Tong University, Xi'an, China guoyoumin163@sina.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000502:physiology*; D047629:Estrogen Receptor beta / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C506487:ESR1 protein, human; C000600034:ESR2 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004958:Estradiol; D002945:Cisplatin