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Updated: Jun 16, 2025
Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
SKF96365 Inhibits Tumor Proliferation by Inducing Apoptosis and Autophagy in Human Esophageal Squamous Cell Carcinoma
Jiaxin Zhang1, Huiqiong Han1, Yihan Liu1
1Department of Oncology The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Abstract:
Calcium channel blockers are emerging as a new generation of attractive anticancer drugs. SKF96365, originally thought to be a store-operated calcium entry (SOCE) inhibitor, is now often used as a TRPC channel blocker and is widely used in medical diagnostics. SKF96365 has shown antitumor effects on a variety of cancer cell lines. The objective of this study was to investigate the anticancer effect of SKF96365 on esophageal cancer in vivo and in vitro. Cell Counting Kit-8 (CCK-8) and colony formation were used to test the proliferation inhibition of SKF96365 on cell lines. Western blot and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to detect cell apoptosis rates. In addition, we demonstrated the antitumor effect of SKF96365 in vivo in xenografted mice. As a result, SKF96365 significantly inhibited the proliferation of K510, K30, and EC9706 in vitro. SKF96365 induces apoptosis in three cell lines through the poly(adenosine diphosphate-ribose) polymerase (PARP), caspase-9, and BCL-2 pathways in a dose-dependent and time-dependent manner. Moreover, SKF96365 treatment also induced apoptosis and inhibited tumor growth in nude mice. The calcium channel TRPC1 was significantly downregulated by SKF96365. Autophagy was also induced during the treatment of SKF96365. In summary, SKF96365 induces apoptosis (PARP, caspase-9, and BCL-2) and autophagy (LC3-A/B) by inhibiting TRPC1 in esophageal cancer cells, thereby inhibiting tumor growth.
Insights
SKF96365, a TRPC channel blocker, effectively inhibits esophageal cancer cell growth and tumor development. It works by inducing apoptosis and autophagy through the TRPC1 pathway, offering a promising new avenue for cancer therapy.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Calcium channel blockers are gaining attention as potential anticancer agents.
- SKF96365, a TRPC channel blocker, has demonstrated antitumor effects across various cancer cell lines.
Purpose of the Study:
- To investigate the anticancer effects of SKF96365 on esophageal cancer, both in vitro and in vivo.
- To elucidate the molecular mechanisms underlying SKF96365's antitumor activity in esophageal cancer.
Main Methods:
- Cell proliferation was assessed using Cell Counting Kit-8 (CCK-8) and colony formation assays.
- Apoptosis was detected via Western blot and TUNEL staining, analyzing pathways like PARP, caspase-9, and BCL-2.
- In vivo efficacy was evaluated in xenografted nude mice models.
Main Results:
- SKF96365 significantly inhibited esophageal cancer cell proliferation in vitro.
- The drug induced apoptosis and autophagy in cancer cells, mediated by the downregulation of TRPC1.
- SKF96365 demonstrated significant antitumor effects in vivo, inhibiting tumor growth in mice.
Conclusions:
- SKF96365 exhibits potent anticancer properties against esophageal cancer by inducing apoptosis and autophagy.
- The mechanism involves the inhibition of TRPC1, impacting key apoptotic and autophagic pathways.
- SKF96365 represents a promising therapeutic candidate for esophageal cancer treatment.
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