title: Bufalin Inhibits HCT116 Colon Cancer Cells and Its Orthotopic Xenograft Tumor in Mice Model through Genes Related to Apoptotic and PTEN/AKT Pathways.
abstract: Aims. To investigate the anticolorectal cancer (CRC) effects of Bufalin, a bioactive polyhydroxysteroid from Venenum Bufonis, using HCT116 human CRC cell and an established orthotopic xenograft model in mice, and to explore the mechanisms of action. Material and Methods. Cultured HCT116 cells or BALB/c mice with orthotopic tumor were treated by Bufalin (positive control: 5-FU). Cell proliferation, apoptosis, and cycling were determined by MTT, Annexin V/PI staining, and flow cytometry, respectively. In mice, tumor inhibition rate and animal survival were calculated. The expressions of PTEN/phosphate-PTEN, AKT/phosphate-AKT, Bad, Bcl-xl, Bax, or Caspase-3 in cells and/or tumors were determined by Western blot or immunohistochemical staining. Results. Bufalin significantly inhibited cell proliferation and induced cell apoptosis and cycle arrest in a dose/time-dependent manner. In the animal model, Bufalin treatment resulted in significant inhibition of tumor growth and prolonged survival. In the Bufalin-treated cultured cells and/or xenograft tumors, the expressions of PTEN, Bad, Bax, and Caspase-3 were significantly increased, while p-AKT and Bcl-xL significantly decreased. Conclusions. Our results indicate that Bufalin inhibit cell proliferation and orthotopic tumor growth by inducing cell apoptosis through the intrinsic apoptotic pathway, which is of pivotal significance in the identification of an anticancer drug that may synergize with Bufalin.
authors.affiliation: Department Surgery, Putuo Hospital, University of Traditional Chinese Medicine in Shanghai, Shanghai 200062, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department Surgery, Putuo Hospital, University of Traditional Chinese Medicine in Shanghai, Shanghai 200062, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department Surgery, Putuo Hospital, University of Traditional Chinese Medicine in Shanghai, Shanghai 200062, China.
authors.forename: Shiying
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department Surgery, Putuo Hospital, University of Traditional Chinese Medicine in Shanghai, Shanghai 200062, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department Surgery, Putuo Hospital, University of Traditional Chinese Medicine in Shanghai, Shanghai 200062, China.
authors.forename: Peihao
authors.initials: P
authors.lastname: Yin
authors.affiliation: Department Surgery, Putuo Hospital, University of Traditional Chinese Medicine in Shanghai, Shanghai 200062, China.
authors.forename: Zhongxiang
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department Surgery, Putuo Hospital, University of Traditional Chinese Medicine in Shanghai, Shanghai 200062, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department Surgery, Putuo Hospital, University of Traditional Chinese Medicine in Shanghai, Shanghai 200062, China.
authors.forename: Dianxu
authors.initials: D
authors.lastname: Feng
authors.affiliation: Department Surgery, Putuo Hospital, University of Traditional Chinese Medicine in Shanghai, Shanghai 200062, China.
authors.forename: Qinsong
authors.initials: Q
authors.lastname: Zuo
authors.affiliation: Department Surgery, Putuo Hospital, University of Traditional Chinese Medicine in Shanghai, Shanghai 200062, China.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department Surgery, Putuo Hospital, University of Traditional Chinese Medicine in Shanghai, Shanghai 200062, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Chen