title: Oral kanglaite injection (KLTI) attenuates the lung cancer-promoting effect of high-fat diet (HFD)-induced obesity.
abstract: Obesity is a risk factor for cancer and cancer-related mortality, however, its role in lung cancer progression remains controversial. This study aimed to assess whether high-fat diet (HFD)-induced obesity promotes lung cancer progression and whether the promotion can be decreased by Kanglaite injection (KLTI). In vivo, HFD-induced overweight or obesity increases the lung carcinoma incidence and multiplicity in a urethane-induced lung carcinogenic model and cancer-related mortality in a LLC allograft model by increasing oxidative stress and cellular signaling molecules including JAK, STAT3, Akt, mTOR, NF-κB and cyclin D1. These changes resulted in increases in vascular disruption and the lung water content, thereby promoting lung epithelial proliferation and the epithelial-mesenchymal transition (EMT) during carcinogenesis. Chronic KLTI treatment substantially prevented the weight gain resulting from HFD consumption, thereby reversing the metabolic dysfunction-related physiological changes and reducing susceptibility to lung carcinogenesis. In vitro, KLTI significantly suppressed the proliferation and induced apoptosis and differentiation in 3T3-L1 preadipocyte cells and attenuated endothelial cell permeability in HUVECs. Our study indicates that there is a potential relationship between obesity and lung cancer. This is the first study to show that obesity can directly accelerate carcinogen-induced lung cancer progression and that KLTI can decrease the lung cancer-promoting effect of HFD-induced obesity.
authors.affiliation: Institute of Pharmacy, Pharmacy College of Henan University, Jinming District, Kaifeng, Henan Province 475004, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Cao
authors.affiliation: Institute of Pharmacy, Pharmacy College of Henan University, Jinming District, Kaifeng, Henan Province 475004, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Ma
authors.affiliation: Institute of Pharmacy, Pharmacy College of Henan University, Jinming District, Kaifeng, Henan Province 475004, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Institute of Pharmacy, Pharmacy College of Henan University, Jinming District, Kaifeng, Henan Province 475004, China.
authors.forename: Yaqiu
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Institute of Pharmacy, Pharmacy College of Henan University, Jinming District, Kaifeng, Henan Province 475004, China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Geng
authors.affiliation: Institute of Pharmacy, Pharmacy College of Henan University, Jinming District, Kaifeng, Henan Province 475004, China.
authors.forename: Mingjing
authors.initials: M
authors.lastname: Meng
authors.affiliation: Institute of Pharmacy, Pharmacy College of Henan University, Jinming District, Kaifeng, Henan Province 475004, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Du
authors.affiliation: Institute of Pharmacy, Pharmacy College of Henan University, Jinming District, Kaifeng, Henan Province 475004, China.
authors.forename: Haihong
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Oncology, The First Hospital Affiliated to Henan University, Kaifeng, Henan Province 475001, China.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Institute of Pharmacy, Pharmacy College of Henan University, Jinming District, Kaifeng, Henan Province 475004, China.
authors.forename: Gangjun
authors.initials: G
authors.lastname: Du
mesh_terms: D016475:3T3 Cells; D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology; D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D018450:Disease Progression; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005951:Glucose Tolerance Test; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009765:Obesity / Q000150:complications*; D050177:Overweight; D018384:Oxidative Stress; D012307:Risk Factors; D015398:Signal Transduction
chemical_list: D004365:Drugs, Chinese Herbal; C499781:kang-lai-te
keywords: cellular signaling molecules; kanglaite injection (KLTI); metabolic dysfunction; overweight and obesity; tissue edema