Smoothened antagonist GDC‑0449 (Vismodegib) inhibits proliferation and triggers apoptosis in colon cancer cell lines

Wu,Chuanqing; Hu,Shaobo; Cheng,Ji; Wang,Guobin; Tao,Kaixiong

doi:10.3892/etm.2017.4282

Smoothened antagonist GDC‑0449 (Vismodegib) inhibits proliferation and triggers apoptosis in colon cancer cell lines

Authors:
- Chuanqing Wu
- Shaobo Hu
- Ji Cheng
- Guobin Wang
- Kaixiong Tao
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Affiliations: Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
Published online on: March 29, 2017 https://doi.org/10.3892/etm.2017.4282
Pages: 2529-2536

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Abstract

The sonic hedgehog (Shh) pathway has been proven to be involved in embryonic development and cancer growth. GDC‑0449, an antagonist of the hedgehog signaling receptor Smoothened (Smo), was recently approved by the US Food and Drug Administration as a prescription for skin basal cell carcinoma. However, the efficacy of GDC‑0449 in the treatment of colon cancer and other malignancies, such as basal cell carcinoma and pancreatic cancer, has remained to be proven. The present study assessed the effect of GDC‑0449 on the colon cancer cell lines Caco‑2 and Ht‑29. A Cell Counting Kit‑8 assay was applied to assess the cell proliferation rate and apoptosis was tested by flow cytometry. Reverse‑transcription quantitative PCR and western blot analysis were used for analyzing expression levels of target genes. Cell proliferation was inhibited, while apoptosis was increased by GDC‑0449, whereas the expression of B‑cell lymphoma 2 (Bcl‑2), a downstream target of Shh signaling, was decreased. Consistent with the inhibition of Gli1 expression, the cancer stem cell markers CD44 and ALDH were decreased in the presence of GDC‑0449. In conclusion, GDC‑0449 was shown to inhibit the replication of colon cancer cells and trigger apoptosis through downregulating Bcl‑2. This may also influence the stemness of cancer stem cells as indicated by the decreased stem cell surface markers.

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