title: Reduced proliferation and increased apoptosis of the SGC‑7901 gastric cancer cell line on exposure to GDC‑0449.
abstract: The sonic hedgehog (Shh) pathway is known to be vital in embryonic development and cancer propagation due to its irreplaceable role in cell proliferation and differentiation. GDC‑0449, a basal cell skin cancer target drug approved by the Food and Drugs Administration, is a smoothened (Smo)-specific antagonist. Although it has been clinically verified as a valid drug for the treatment of skin and pancreatic cancer, the application of GDC‑0449 in gastric cancer requires further investigation. In the present study, high-glucose Dulbecco's modified Eagle's medium with 10% fetal bovine serum was used for routine SGC‑7901 cell line culture. A Cell Counting Kit‑8 assay was employed for determination of the reproductive rate of the cells. Flow cytometry was performed to determine the apoptosis status of the SGC‑7901 cell line through Q4 analysis. Reverse transcription-quantitative polymerase chain reaction and Western blot analyses were used as target molecule detection vehicles. As expected, GDC‑0449 reduced the expression levels of Shh‑associated molecules, including Smo and gli1, compared with the blank group. The rate of cell proliferation was markedly limited and was accompanied by an increase in the apoptotic rate following GDC‑0449 exposure. In addition, further investigations confirmed B cell lymphoma‑2 (Bcl‑2) as the downstream molecular mechanism of GDC‑0449 efficacy. Of note, representatives of the cancer stem cell (CSC) surface marker, CD44 and CD133, demonstrated a similar trend to the Smo restriction observed. By repressing the expression of Bcl‑2, GDC‑0449 inhibited the normal proliferation of SGC‑7901 cells, and accelerated the apoptotic rate of the cells. It may also alter CSC properties due to the reduction in the expression of surface markers.
authors.affiliation: Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Chuanqing
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Ji
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Deng
authors.affiliation: Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Yamba Willy
authors.initials: YW
authors.lastname: Muangu
authors.affiliation: Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Weilong
authors.initials: W
authors.lastname: Chang
authors.affiliation: Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Guobin
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Kaixiong
authors.initials: K
authors.lastname: Tao
mesh_terms: D000813:Anilides / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000072086:Smoothened Receptor; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D000813:Anilides; D014408:Biomarkers, Tumor; D053823:Hedgehog Proteins; C538724:HhAntag691; D019253:Proto-Oncogene Proteins c-bcl-2; D011725:Pyridines; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor