Effects of Sophora flavescens aiton and the absorbed bioactive metabolite matrine individually and in combination with 5-fluorouracil on proliferation and apoptosis of gastric cancer cells in nude mice

Abstract

Background:Sophora flavescens aiton (SFA) and its main bioactive metabolite matrine are widely used in traditional Chinese medicine (TCM) preparations and have achieved good curative effects for the treatment of various tumors. However, the mechanisms underlying SFA and matrine individually and in combination with chemotherapeutic drugs for treatment of gastric cancer (GC) remain unclear.Aim of the study: To elucidate the mechanisms underlying the ability of SFA and matrine individually and in combination with chemotherapeutic drugs to inhibit proliferation and promote apoptosis of human GC cells.Materials and methods: Forty-eight nude mice were randomly divided into six groups that were treated with normal saline (model group), 5-fluorouracil (5-FU), SFA decoction (SFAD), matrine, SFAD+5-FU, or matrine+5-FU. A subcutaneous heterotopic tumor model was established in nude mice by implantation of human GC BGC-823 cells. All mice were treated for 28 days. Bioactive metabolites in SFA were determined by HPLC-MS/MS. The tumor volume, tumor weight, and tumor inhibition rate of mice were documented. Histopathology and ultramicroscopic pathology of tumor tissues were observed. The tumor cell cycle and apoptosis in vivo were detected. Serum levels of PCNA, BAX, Bcl-2, Caspase-9, Caspase-3 and cleaved Caspase-3 were measured. Protein levels of MS4A10, MS4A8, MS4A7, PCNA, BAX, Bcl-2, Caspase-3, and cleaved Caspase-3 were measured in tumor tissues.Results: Both SFAD and matrine inhibited the growth of transplanted GC cells, which was more effective when combined with 5-FU. The tumor inhibition rates of the 5-FU, SFAD, matrine, SFAD+5-FU, and matrine+5-FU groups were 53.85%, 33.96%, 30.44%, 59.74%, and 56.55%, respectively. The body weight of tumor-bearing nude mice was greater in the SFAD group than the normal saline and matrine groups. SFAD+5-FU and matrine+5-FU blocked BGC-823 cells in the G0-G1/S transition, promoted apoptosis, and significantly decreased the content of serum apoptosis-inhibitory proteins (PCNA and Bcl-2) as well as protein expression of MS4A8, MS4A10, Bcl-2, and PCNA in tumor tissues, while increasing serum levels of pro-apoptotic proteins (Caspase-9, Caspase-3 and cleaved-Caspase-3) and protein expression of BAX and cleaved-Caspase-3 in tumor tissues.Conclusion: SFAD and matrine both individually and in combination with 5-FU ameliorated malignancy of transplanted tumors by reducing proliferation and promoting apoptosis of BGC-823 cells. These findings confirm the anti-tumor synergistic effect of TCM and chemotherapeutic drugs.

Assessment of chemotherapy resistance changes in human colorectal cancer xenografts in rats based on MRI histogram features

“…Therefore, it is urgent to find a relatively accurate and comprehensive non-invasive method for drug resistance assessment of colorectal cancer. The nude mouse model of colorectal cancer transplantation can well reflect the pathological characteristics of human colorectal cancer, and it is well controlled in the experiment ( 7 ).…”

Liquid chromatography-tandem mass spectrometry analysis of a ratio-optimized drug pair of Sophora flavescens Aiton and Coptis chinensis Franch and study on the mechanism of anti-colorectal cancer effect of two alkaloids thereof

“…The earliest use of this drug pair was recorded in the Prescriptions for Universal Relief (Pujifang). In addition, it has been reported that Kushen and Huanglian exert good curative effects in the treatment of tumors ( 39 , 40 ). Matrine and berberine are two alkaloids contained in Kushen and Huanglian, respectively ( 41 , 42 ).…”

Oxymatrine Alleviates Collagen-Induced Arthritis in Mice by Regulating the Immune Balance of T Cells

“…Sophora flavescens has been reported to clear heat and remove dampness, which has antibacterial and anti-inflammatory effects [4]. OMT, as one of the major bioactive components in Sophora flavescens, has a wide range of pharmacological and biological activities [5], including antibacterial [6], antiviral, antioxidant, anti-tumor [7], and other effects [8]. Our team previously found that OMT can alleviate collagen induced arthritis by reducing the abundance of Tfh cells in the spleen, thereby reducing the production of autoantibodies.…”