J Cancer 2018; 9(1):32-40. doi:10.7150/jca.21224
Efficacy of Shikonin against Esophageal Cancer Cells and its possible mechanisms in vitro and in vivo
1. Department of Biochemistry;
2. School of Pharmacy;
3. Department of Pharmacy, Nan Chong Central Hospital;
4. Pathogenic Biology and Immunology Experiment Teaching Center, North of Si Chuan Medical University, China.
*Jian-Cai Tang and Jia Zhao contributed equally to this work.
Increasing evidences indicate that shikonin can suppress the tumor growth. However, the mechanisms remain elusive. In the present study, we investigated the effects and mechanisms of shikonin against esophageal cancer. The expression of hypoxia inducible factor 1α (HIF1α) and pyruvate kinase M2 (PKM2) in esophageal cancer tissues and cells was detected by immunohistochemistry and Western blot. CCK-8 was used to examine the esophageal cancer cell viability. Apoptosis and cell cycle were analyzed by flow cytometry. The expression of EGFR, PI3K, Akt, p-AKT, mTOR, HIF1α and PKM2 was detected by Western blot. EC109/pkm2 was established by lentivirus transducer. Ec109 tumor model was founded to observe the antitumor effect of shikonin in vivo.
We found that HIF1α and PKM2 protein expression levels were higher in esophageal cancer tissues and cells than normal esophageal tissues and cells. Shikonin reduced esophageal cancer cells viability and induced cell cycle arrest and apoptosis. Shikonin decreased EGFR, PI3K, p-AKT, HIF1α and PKM2 expression. Overexpression of PKM2 could enhance resistance of esophageal cancer cells to shikonin. In vivo we found that shikonin reduced tumor burden, inducing cell arrest and apoptosis. Taken together, shikonin has a significant antitumor effect in the esophageal cancer by regulating HIF1α/PKM2 signal pathway.
Keywords: Shikonin, Esohpageal cancer, hypoxia inducible factor 1α, Pyruvate kinase M2, CyclinD1
Tang JC, Zhao J, Long F, Chen Jy, Mu B, Jiang Z, Ren Y, Yang J. Efficacy of Shikonin against Esophageal Cancer Cells and its possible mechanisms in vitro and in vivo. J Cancer 2018; 9(1):32-40. doi:10.7150/jca.21224. Available from http://www.jcancer.org/v09p0032.htm