Experimental Study On The Anti-cervical Cancer Effect Of Five Ferula Species In Xinjiang

Objective:to observe the inhibitory effect of five species of Ferula sinkiangensis on the proliferation of mouse cervical cancer U14 cells and human breast cancer MCF-7 cells in vitro,and to establish the GC-MS fingerprints of four petroleum ether fractions of Ferula sinkiangensis The acute toxicity experiment of 5 species of Ferula in Xinjiang and the effect of 5 species of Ferula in Xinjiang on U14 ectopic tumor in mice with cervical carcinoma were observed in Vivo.Methods:1.Ethanol extracts and petroleum ether fractions from 5 species of Ferula sinkiangensis were used to interfere with U14 cells of mice and MCF-7 cells of human breast cancer at different concentrations.The OD values were determined by MTT colorimetry,the rate of tumor cell proliferation inhibition was calculated.2.The petroleum ether fraction of four species of Ferula in Xinjiang was extracted by organic solvent,and the chemical components in the petroleum ether fraction were analyzed by GC-MS fingerprint.3.The acute toxicity experiment of ethanol extracts from 5 species of Ferula in Xinjiang on mice was carried out,and the maximum tolerance multiple of mice was calculated.4.To establish the tumor model of U14 heterotopic tumor in mice with cervical cancer,the mice were randomly divided into blank group,model group,cisplatin group,Ferula high-dose Group and low-dose Group,tissue samples from the tumor,spleen,kidney and Thymus were taken,organ index,tumor inhibition rate and serum levels of Alanine transaminase,creatinine and Cystatin C were calculated.Results:1.?1?The inhibitory effects of ethanol extracts from five species of Ferula sinkiangensis on the proliferation of U14 cells in mice were as follows:Ferula krylovii>Ferula sinkiangensis>Ferula lehmannii>Ferula fukanensis>Ferula conocaula,the IC₅₀ values of ethanol extracts from Ferula krylovii,Ferula sinkiangensis and Ferula lehmannii were69.09 mg/L,73.90 mg/L and 83.18 mg/L respectively.The inhibitory effects of five petroleum ether fractions of Asafetida on the proliferation of mouse cervical cancer U14cells were as follows:Ferula sinkiangensis>Ferula lehmannii>Ferula krylovii>Ferula conocaula>Ferula fukanensis,The IC₅₀0 values of petroleum ether fractions from Ferula sinkiangensis,Ferula lehmannii and Ferula krylovi were 45.84 mg/L,52.85 mg/L and63.81 mg/L respectively.?2?The inhibitory effects of ethanol extracts from five species of Asafetida in Xinjiang on the proliferation of Human Breast Cancer Cell Line MCF-7 were as follows:Ferula sinkiangensis>Ferula lehmannii>Ferula krylovii>Ferula fukanensis>Ferula conocaula,the IC₅₀0 of ethanol extracts from Ferula sinkiangensis,Ferula lehmannii and Ferula krylovi were 24.98 mg/L,69.26 mg/L and 98.99 mg/L respectively.The inhibitory effects of five petroleum ether fractions of Asafetida on the proliferation of Human Breast Cancer Cell Line MCF-7 were as follows:Ferula sinkiangensis>Ferula lehmannii>Ferula krylovii>Ferula conocaula>Ferula fukanensis,the IC₅₀ values of petroleum ether fractions from Ferula sinkiangensis,Ferula lehmannii and Ferula krylovi were 20.46 mg/L,32.83 mg/L and 72.67 mg/L respectively.2.fifty-five chromatographic peaks were detected in petroleum ether from Ferula sinkiangensis,and 52 compounds were identified.The highest content of the compounds was 24-decylenol-3,12-diene?8.55%?;A total of 49 chromatogram peaks were detected in petroleum ether from Ferula fukanensis,and all compounds were identified.The content of stigmasterol was the highest?9.64%?;while 50 chromatogram peaks were detected in petroleum ether from Ferula conocaula,and all compounds were identified,the content of stigmasterol was the highest?13.02%?;58 peaks were detected in petroleum ether from Ferula krylovii,and 55 compounds were identified,of which progesterone was the highest?23.02%?.3.The maximum tolerance of ethanol extracts from 5 species of Ferula in Xinjiang was 120 times that of adult mice.4.?1?compared with the model group,the high-dose and low-dose groups of ethanol extracts from Ferula lehmannii,Ferula conocaula and Ferula sinkiangensis showed significant antitumor effects,with tumor inhibition rates of 87.23%,74.47%,70.21%,87.23%,61.70%and 89.36%respectively.?2?compared with blank group,there was no significant difference in spleen and kidney weight and index between high and low dose groups?P>0.05?.The thymus weight and thymus index increased in low dose group with significant difference?P<0.05?.?3?compared with the blank group,there was no significant difference in the Alanine transaminase and creatinine between the high and low dose groups?P>0.05?.The value of Cystatin C in Ferula krylovii High Dose Group was significantly lower than that in control group?P<0.05?.Conclusion:1.The proliferation of U14 cells and MCF-7 cells,including Ferula krylovii,Ferula sinkiangensis and Ferula lehmannii was inhibited by ethanol extract and petroleum ether,the inhibitory effect of Ferula conocaula and Ferula fukanensis is relatively weak.2.The majority of the petroleum ether fraction in Ferula sinkiangensis was diene,and the majority of the petroleum ether fraction in Ferula fukanensis and Ferula conocaula were sterols,the highest concentrations of ketones are found in petroleum ether from Ferula krylovii.3.According to the alcohol extract of five kinds of Ferula in Xinjiang,the maximum tolerance multiple of mice is 120 times that of adults,and there is no poisoning or death in mice and it is more than 100 times,so the maximum tolerance multiple of this experiment is the safe dose.4.?1?Ferula lehmannii,Ferula conocaula and ethanol extracts from Ferula sinkiangensis have significant antitumor effects.?2?compared with the blank group,5 kinds of ethanol extracts of Ferula had no effect on the weight of spleen,kidney,thymus gland and its index,liver function and renal function.