ABSTRACT
BACKGROUND: "Collateral disease theory", as an important theory of traditional Chinese medicine, is often used in the clinical treatment of tumors, showing a remarkable effect, especially in advanced malignancies with blood stasis and toxin. METHODS: In this study, we analyzed 5 cases of advanced malignancies, and discussed the efficacy of collateral disease theory in advanced malignancies with blood stasis and toxin. The 5 cases were suffered from right lung squamous cell carcinoma, left lung squamous cell carcinoma, stage IV endometrial carcinoma, right submandibular lymphatic follicular lymphoma and right lower lung cancer, respectively. Combining with the pathogenesis of collateral disease in traditional Chinese medicine dialectically and taking insect medicine as an example, traditional Chinese medicine was prescribed. Furthermore, the application effect of "collateral disease theory" in malignancy with blood stasis and toxin was explored. RESULTS: After treated with traditional Chinese medicine, the tumor lesions in the 5 cases were reduced to varying degrees. CONCLUSION: The treatment based on "collateral disease theory" is effective for advanced malignancy with blood stasis and toxin, but this finding needs to be verified by prospective studies.
ABSTRACT
Background: Irinotecan (also known as CPT-11) is a topoisomerase I inhibitor that is primarily used for the treatment of advanced colorectal cancer. CPT-11 and its active metabolite SN-38 can directly damage intestinal mucosal cells. In addition, CPT-11 can activate the Toll-like receptor 4 (TLR4) inflammasome/nuclear factor kappa-B p65 (NF-κB p65) pathway, ultimately leading to intestinal inflammation-related injury. Shu Bu Wenshen Guchang recipe (SBWGR) has the spleen and kidneys. Herein, we investigated the effects of SBWGR on intestinal injury and the TLR4/NF-κB signaling pathways in mice with CPT-11-induced delayed-type diarrhea, aiming to provide evidence for the treatment of CPT-11-induced delayed-type diarrhea. Methods: Thirty tumor-bearing mice were divided into normal control, model control, octreotide, low dose SBWGR, and high dose SBWGR groups, with 6 mice in each group. After successful modelling of delayed diarrhea, the normal and model control groups were given equal amounts of saline for 5 consecutive days, and the other three groups gave the corresponding intra-drug administration. Body weight, tumor size, Chiu score, intestinal ischemia and reperfusion injury, and disease activity index (DAI) were recorded in each group. The levels of intestinal interleukin-1ß (IL-1ß), IL-18, and tumor necrosis factor-α (TNF-α) were measured by an enzyme-linked immunosorbent assay (ELISA). Intestinal TLR4 and NF-κB p65 levels were measured by reverse transcription-polymerase chain reaction (RT-PCR) and protein blotting. Results: The weight of octreotide and kidney was higher than the control group (P<0.05); The tumor volume comparison of the model control group, octreotide group, warm kidney intestine low dose group, and warm kidney intestine high dose group were not significantly different (P>0.05). Octreotide group, intestinal Chiu score, diarrhea score, DAI level, intestinal inflammatory cytokines, IL-1ß, IL-18 and TNF-α intestinal level, intestinal TLR4, NF-κB p65 mRNA protein expression levels were significantly lower than those of the model control group (P<0.05), and the amount of the treatment group was increased (P<0.05). Conclusions: SBWGR exerts a prominent protective effect on intestinal damage caused by CPT-11-induced delayed-type diarrhea, which may be achieved by inhibiting the activation of the intestinal TLR4/NF-κB signaling pathway.
ABSTRACT
To elucidate regulatory effects and molecular mechanisms of diosgenin on colon cancer, this study administered diosgenin at concentrations of 10 (low), 50 (medium), and 100 µmol/L (high concentration group) at the cell level, respectively. EdU, colony formation, and Transwell assays were implemented to determine SW480 cellular proliferation and migration. Assays of flow cytometry and TUNEL were employed to estimate cell apoptosis. Additionally, nude mouse tumorigenesis assay was used to further verify the regulatory function of diosgenin on colon cancer. The target protein of diosgenin was predicted via molecular docking. The results showed that all three concentrations of diosgenin could reduce colon cancer cellular proliferation and migration, and after diosgenin treatment, colon cancer cellular apoptosis was markedly increased, and the 100 µmol/L diosgenin group produced the most satisfactory inhibition on colon cancer cell proliferation. Ki67 expression was markedly reduced whereas those of Bax and caspase3 were greatly increased after diosgenin treatment. The nude mouse tumorigenesis assay indicated that the parameters of tumorous volume and mass of diosgenin treatment group were greatly decreased as compared to control, and as the concentration of diosgenin increased, the inhibitory effect was more significant. Molecular docking indicated that STAT3 served as a target protein of diosgenin. Moreover, after diosgenin treatment on colon cancer cells, the STAT3 expression was markedly reduced. The STAT3 overexpression would counteract the inhibitory effect of 50 µmol/L diosgenin in both suppressing colon cancer cellular proliferation and migration and promoting apoptosis. Taken together, all our outcomes demonstrated the diosgenin effects in not only inhibiting colon cancer cellular proliferation and migration but also promoting cancerous cellular apoptosis. Diosgenin is a regulatory player in targeting and regulating STAT3.
