Abstract: Objective To explore the molecular mechanisms by which mitochondrial estrogen receptor β (ERβ) suppresses
non-small cell lung cancer cell apoptosis induced by apoptotic stimulations. Methods The mitochondrial localization of ERβ in
non-small cell lung cancer cell lines A549 and 201T was determined using immunofluorescence and Western blotting. The
changes of apoptosis of the cells with mitochondrial ERβ overexpression or knockdown in response to cisplatin and STS
treatments were assessed, and mitochondrial ERβ interaction with the pro-apoptotic protein Bad was detected using
co-immunoprecipitation and Western blotting. Results ERβ was localized in the mitochondria in A549 and 201T cells. ERβ
overexpression significantly reduced while ERβ knockdown increased Bax activation and cell apoptosis induced by cisplatin
and STS. Mitochondrial ERβ interaction with pro-apoptotic protein Bad may suppress Bax activation and its translocation to
the mitochondria. Conclusion Mitochondrial ERβ can suppress apoptosis of non-small cell lung cancer cells induced by
cisplatin or STS through interaction with Bad, suggesting the value of mitochondrial ERβ as a new therapeutic target for
treatment of non-small cell lung cancer.