Open AccessGinsenoside Rb3 Alleviates the Toxic Effect of Cisplatin on the Kidney during Its Treatment to Oral Cancer via TGF-β-Mediated Mitochondrial Apoptosis
Author(s) -
Wenjie Wu,
Yufang Tang,
Shuang Dong,
Jie Zhang
Publication year - 2021
Publication title -
evidence-based complementary and alternative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.552
H-Index - 90
eISSN - 1741-4288
pISSN - 1741-427X
DOI - 10.1155/2021/6640714
Subject(s) - apoptosis , blot , flow cytometry , cisplatin , kidney , microbiology and biotechnology , caspase 3 , cancer research , inner mitochondrial membrane , chemistry , biology , pharmacology , medicine , programmed cell death , endocrinology , biochemistry , chemotherapy , gene
Objective The research aimed to confirm the role of the transforming growth factor- β (TGF- β ) in cisplatin- (CPT-) evoked kidney toxicity and elucidate the mechanism that ginsenoside Rb3 (Rb3) could alleviate the kidney toxicity by CPT during its treatment to oral cancer via TGF- β -mediated mitochondrial apoptosis.Methods The model of xenograft nude mice bearing oral carcinoma cells ACC83 was established and treated with CPT and/or Rb3, respectively. Bodyweights of the treated mice were weighed, and the kidney tissues were collected; following, the histopathology and the expression of TGF- β were examined using H&E staining and immunohistochemistry. Afterward, the renal cells GP-293 were treated with CPT and/or Rb3. The expression and phosphoration of TGF- β , Smad2, Smad3, Bcl-2, and Bax in GP-293 cells were detected by Western blotting. The cellular apoptosis and mitochondrial membrane potential were analyzed using flow cytometry.Results The xenograft nude mice exposure to CPT presented the bodyweight loss, necrotic areas, and the increased expression of TGF in kidney tissue, and Rb3 pretreatment relieved these changes evoked by CPT. In GP-293 cells, CPT administration induced the phosphorylation of Smad2 and Smad3, and Rb3 pretreatment suppressed the induced phosphorylation by CPT. Besides, flow cytometry analysis showed that Rb3 inhibited the CPT-evoked cellular apoptosis ratio and mitochondrial membrane depolarization. The Western blotting test indicated that Rb3 alleviated the cleavage of PARP, caspase 3, caspase 8, and caspase 9, the induction of Bax expression, and inhibition of Bcl-2 expression. Additionally, after treating with the TGF inhibitor of disitertide, Rb3 exhibited no alleviation effects on CPT-evoked cellular apoptosis ratio, inhibition of Bax expression, and induction of Bcl-2 expression in GP-293 cells.Conclusion Rb3 could alleviate CPT-evoked toxic effects on kidney cells during its treatment to oral cancer via TGF- β -mediated mitochondrial apoptosis.