| BackgroundAlthough the diagnosis and treatment of malignant tumors have made rapid progress,both radiotherapy and chemotherapy,targeted therapy and immunotherapy,drug resistance and side effects are the bottlenecks that restrict the clinical treatment effect.[1].According to statistics,about one-third of cancer patients die from various side effects caused by radiotherapy and chemotherapy,mainly due to immune function inhibition and tissue and organ damage caused by decreased immunity,which seriously affects the quality of life of patients[1].Kidney injury is a common toxic side effect of many first-line chemotherapy drugs,such as docetaxel,cisplatin and doxorubicin[3].When the kidney is damaged,waste products will accumulate in the body,which may lead to death in severe cases[1].Cisplatin is a broad-spectrum anticancer drug used to treat a variety of rapidly growing solid tumors,such as non-small cell lung cancer[5].However,cisplatin has a series of toxic side effects.Among these side effects,acute kidney injury(AKI)is the main cause,and the degree of kidney damage is positively correlated with the dose of cisplatin[6,7].In order to alleviate the toxic side effects of drugs and improve the efficacy of the drugs,the combination of drugs,drug selectivity or auxiliary drugs are effective means for alleviating or reducing the side effects of drugs.Natural products have a wide variety,novel structure,multiple targets and multiple pathways,small toxic and side effects,and diverse biological activities[8].They are not only an important resource for the development of new drugs,but also for disease-assisted treatment,immunity,and toxicity reduction.The existing research results show that a variety of natural products derived from traditional Chinese medicine have immunomodulatory effects and play an important role in the treatment of major diseases such as tumors and autoimmune diseases[9].Using the characteristics of natural products,we have screened and found SOP natural mixed components with no obvious side effects,and can significantly reduce the side effects of chemotherapy drugs.This paper will analyze the basic function of natural hydrolysate SOP in tumor-bearing mice,and whether its combination with chemotherapeutic drug cisplatin can reduce its renal toxicity,and initially explore its mechanism of action.ResultsPart I Analysis of the attenuation and synergism of natural hydrolysate SOP1.Selection of chemotherapeutic drugsChemotherapy drugs docetaxel and cisplatin are clinical first-line anti-tumor drugs for lung cancer,breast cancer,prostate cancer,etc.For prostate cancer,docetaxel is the only moderate A drug that improves survival.But they also have serious toxic side effects,such as immune function inhibition and tissue and organ damage.We first used prostate cancer and lung cancer as models to analyze the effects of SOP on the efficacy and toxicity of docetaxel and cisplatin.2.Toxicity analysis of SOPThe tumor-bearing mice were used to analyze the toxicity of SOP.The C57BL/6 xenograft tumor-bearing mouse model was constructed by subcutaneous inoculation of mouse prostate cancer cells RM1 and mouse lung cancer LLC cells.The weight and status are the same as normal mice,indicating that SOP is not toxic to the body.3.The synergistic effect of SOP on chemotherapeutic drugsFor the single-use chemotherapy drug docetaxel,the tumor inhibition rate is 65.3%,combined with SOP,the tumor inhibition rate is 59.3%,which basically does not affect the anti-tumor effect of docetaxel.The chemotherapy drug cisplatin alone,the tumor inhibition rate was 74.3%,combined with SOP,the tumor inhibition rate was 72.8%,which did not affect the antitumor effect of chemotherapy drugs.4.The effect of SOP on the toxicity of chemotherapy drugsBy detecting liver(AST and ALT)and kidney(CR and BUN)functional indicators,there was no significant change in ALT and AST in each group,and BUN and CR in cisplatin group were significantly increased.BUN and CR have been significantly reduced.It shows that SOP has a more obvious effect on nephrotoxicity.5.The immune mechanism of SOP attenuation and synergyThrough tissue HE staining,it was found that the level of inflammation decreased after the combination of SOP,by detecting the basic immune indexes of T lymphocytes CD3+,CD4+,CD8+ and macrophages F4/80,CD11b,The combined drug group CD8+ was lower than the control group,CD3 +,CD4 +,CD4 +/CD8 +was higher than the control group,and the macrophage content of the combination group was higher than that of the chemotherapy group,indicating that SOP can stimulate the body immunity.Part ? The mechanism of natural hydrolysate SOP in acute renal injury1.Establishment of acute kidney injury modelAccording to literature review,we use the intraperitoneal injection of different doses of cisplatin,a one-time,effect of different time to find the most suitable dosage and time to build a successful model of acute renal injury in mice.So in the follow-up research through detecting the serum urea nitrogen(BUN),creatinine(CR)and the test results and the observation of the state of renal pathology in mice,we successfully build the model of acute renal injury in mice with 15 mg/kg dose of cisplatin intraperitoneal injection of one-off effect five days,for our follow-up mechanism research.2.Study on the mechanism of natural hydrolysate SOP in acute renal injuryKidney tissue damage caused by cisplatin,serum BUN and CR content decreased significantly,after using the SOP,BUN and CR content has significant statistical differences by qPCR detection of various cytokines levels.We find that certain anti-inflammatory factor levels,inflammatory factor levels drop.therefore,natural hydrolyzate SOP kidney damage caused by cisplatin effective has certain protective effect,it may be through the expression of cytokines to regulate.Conclusion1.As a natural product that can be taken orally and is safe and non-toxic,SOP can be combined with docetaxel and cisplatin,which has a certain synergistic effect,significantly inhibits the toxic and side effects caused by the drug,and significantly improves the quality of life of mice.2.The activation of SOP on the immune system may be one of the mechanisms by which chemotherapeutic drugs can reduce toxicity and enhance efficacy.3.Natural hydrolysate SOP can protect kidney damage in cisplatin-induced acute kidney injury model.Innovation and deficiency1.Innovation:(1)Natural product SOP is a newly discovered product that can be taken orally and is safe and non-toxic.Its combination with chemotherapy drugs is also a new attempt.In the process of combination,it is found that it can improve the immune system,the quality of life and protect kidney and other functions.(2)The mechanism of natural product SOP in immunity and protection of renal function is also first correlated.(3)SOP has a significant protective effect on acute kidney injury induced by cisplatin.2.Shortcomings:(1)the mechanism of synergistic combination of docetaxel and cisplatin by SOP still needs to be further explored,especially the study on the immune mechanism under tumor-bearing pathological conditions is not detailed.(2)under normal physiological conditions,the effect of SOP on the immune system was not analyzed... |
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