title: Salvianolic acid B reverses multidrug resistance in HCT‑8/VCR human colorectal cancer cells by increasing ROS levels.
abstract: Salvianolic acid B (SalB) a water‑soluble phenolic compound, extracted from Salvia miltiorrhiza, has previously been demonstrated to reverse tumor multidrug resistance (MDR), including in colorectal cancer. Reactive oxygen species (ROS) are oxygen radicals generated during aerobic metabolism (superoxide and hydroxyl radicals) and superoxide easily generating free radicals (H2O2). The concept that increased ROS levels can lead to augmented tumor cell‑sensitivity to chemotherapy drugs has become notable. The aim of the present study was to elucidate the role of ROS in mediating the effect of SalB on drug resistance and the correlation with drug resistance‑associated protein, P‑glycoprotein (P‑gp), and apoptosis‑associated proteins, B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X (Bax). In the current study, through utilizing the multidrug resistant colorectal cancer cell line, HCT‑8/VCR, it was demonstrate that SalB reversed MDR in HCT‑8/VCR. In addition, SalB significantly increased ROS levels, which may have accelerated the apoptosis of HCT‑8/VCR cells by downregulating Bcl‑2 and increasing Bax protein expression. Furthermore the increased intracellular ROS levels may have inhibited P‑gp expression at the gene and protein levels. In conclusion, the data of the current study demonstrate that SalB reversed MDR in HCT‑8/VCR cells, and the effect is associated with increased ROS levels, which may downregulate P‑gp expression and promote tumor cell apoptosis, which in turn increases the sensitivity of drug‑resistant cells to chemotherapy drugs.
authors.affiliation: Department of Traditional Chinese Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, P.R. China.
authors.forename: Piaoting
authors.initials: P
authors.lastname: Guo
authors.affiliation: Department of Traditional Chinese Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, P.R. China.
authors.forename: Songpo
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Traditional Chinese Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of Gynecology, Shuguang Hospital Affiliated with Shanghai University of T.C.M, Shanghai 200240, P.R. China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Traditional Chinese Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, P.R. China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Traditional Chinese Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, P.R. China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Traditional Chinese Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, P.R. China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Liu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000111:Acetylcysteine / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D001572:Benzofurans / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D053630:Depsides
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000111:Acetylcysteine; D000970:Antineoplastic Agents; D001572:Benzofurans; D004365:Drugs, Chinese Herbal; D006861:Hydrogen Peroxide; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C076944:salvianolic acid B; D053630:Depsides