Salvianolic acid B reverses multidrug resistance in nude mice bearing human colon cancer stem cells

Abstract

Salvianolic acid B (SalB) is a water-soluble phenolic compound, extractable from Salvia miltiorrhiza, and has previously been demonstrated to reverse tumor multidrug resistance (MDR) in colon cancer cells. Cancer stem cells (CSCs) are closely associated with drug resistance. Therefore, establishing a nude mouse model bearing human colon CSCs is important for the study of the mechanisms underlying colon cancer drug resistance as well as the reversal of drug resistance. The present study aimed to establish a nude mouse model bearing human colon CSCs and to investigate the effects of SalB on the drug resistance exhibited by the nude mouse model as well as determine its underlying mechanism. Cells from two colon cancer cell lines (LoVo and HCT-116) were cultured in serum-free medium to obtain CSCs-enriched spheroid cells. Following this, nude mice were transplanted with LoVo and HCT-116 colon CSCs to establish the CSC nude mouse model, which was subsequently demonstrated to exhibit MDR. The results of the present study revealed that following treatment with SalB, the chemotherapeutic drug resistance of xenografts was reversed to a certain extent. Western blot analysis was performed to investigate the expression levels of cluster of differentiation (CD)44, CD133, transcription factor sox-2 (SOX2) and ATP-binding cassette sub-family G member 2 (ABCG2) proteins, and the results demonstrated that treatment with SalB downregulated the expression of CD44, SOX2 and ABCG2 proteins in both LoVo and HCT-116 colon CSCs xenografts. In conclusion, the results of the present study revealed that a serum-free suspension method can be performed to successfully isolate colon CSCs. In addition, a nude mice bearing colon CSCs animal model was successfully established, and associated tumors were confirmed to exhibit MDR. Furthermore, SalB was demonstrated to successfully reverse MDR in nude mice bearing LoVo and HCT-116 colon CSCs, as well as suppress the expression of CD44, SOX2 and ABCG2 proteins.

Long noncoding RNA STCAT16 suppresses cell growth and its expression predicts prognosis in patients with gastric cancer

“…no. C0105; Beyotime Institute of Biotechnology) as previously described (26), and examined using a light microscope (BX51; Olympus Corporation; magnification, ×400). The nuclear was stained blue and cytoplasm was stained red.…”

Salvianolic Acids: Potential Source of Natural Drugs for the Treatment of Fibrosis Disease and Cancer

“…In addition, Danshensu, an active component of salvianolic acids, inhibited the development of melanoma by affecting tumor angiogenesis and tumor invasion (Zhang et al, 2010). Guo et al (2018) demonstrated that Sal B reversed tumor MDR by down-regulating the expression of CD44, SOX2 and ABCG2 proteins in LoVo and HCT-116 colonic CSC xenografts. A recent study by Wu et al (2018) indicated that S. miltiorrhiza extract inhibited hepatocarcinogenesis by modulating TGF-β/TβR and Imp7/8 protein expression, suggesting that S. miltiorrhiza has multiple targets in HCC treatment.…”

Combination of Chinese and western medicine to prevent and reverse resistance of cancer cells to anticancer drugs

“…在 乳腺癌中, 丹酚酸A能够下调transgelin 2的表达, 逆转 乳腺癌对紫杉醇的耐药 [99,100] . 在结肠癌中, 丹酚酸B能 够抑制肿瘤干细胞的活性, 逆转结肠癌的多药耐药 [101] . 藤黄酸(gambogic acid)是中药藤黄的主要活性成 分.…”