Background Lung cancer is one of the most lethal cancers worldwide. Cisplatin, a widely used anti‐lung cancer drug, has been limited in clinical application due to its drug resistance. Medicines targeting mitochondrial electron transport chain (ETC) complexes may be effective candidates for cisplatin‐based chemotherapy. Methods In this study, the small molecule drug library from Food and Drug Administration FDA was used to screen for medicines targeting ETC. MTT and colony formation assays were used to investigate cell proliferation. Flow cytometry was employed to analyze cell cycle, apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential. Wound scratch and transwell assays were used to detect migration and invasion abilities. The activities of the ETC complex were tested using kits. Western blot analysis was used to investigate the expressions of related proteins. A mouse xenograft model was constructed to verify the antitumor effect in vivo. Results The results showed that mubritinib can reduce the activation of the PI3K/mTOR signal pathway, disrupt mitochondrial function, significantly increase ROS levels and induce oxidative stress, and ultimately exert its antitumor effect against non‐small cell lung cancer (NSCLC) both in vivo and in vitro. In addition, the combination of cisplatin and mubritinib can improve the tumor‐suppressive effect of cisplatin. Conclusion Mubritinib can upregulate intracellular ROS concentration and cell apoptosis, inhibit the PI3K signaling pathway and interfere with the function of mitochondria, thus reducing cell proliferation and increasing ROS induced apoptosis by reducing the activation of Nrf2 by PI3K.

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This study attempts to interpret the urban form of the Japanese cities through the natural spatial reference of front and back which is deeply rooted in Japanese culture. The aim is to provide workable guidance for interpreting the urban form, and for creating diverse and active commercial spaces in Japan and beyond. Based on the physical built environment, this study proposes a parameter of interface which is defined by components taken from both surface of the building and the objects around. The interface is categorized into four types by the combination of main-component of front (F)/back (B) and sub-component of front (f)/back (b), namely Ff, Fb, Bf, and Bb. The approach is demonstrated in the typical commercial district of Shibuya, Tokyo. By analyzing the distributional features of the interface quantitatively, the scopes and attributes of front and back-side space are figured out. According to the distributional similarity of the interface, we sort the urban space into front-side space defined by Ff and back-side space defined by Fb, Bf, and Bb. Thereinto, the ambiguous back-side space defined by Fb and Bf supports diverse possibilities and highly involves in the everyday life of Japanese people.