OBJECTIVES: To investigate the molecular mechanism by which Lichong Xiaozheng Granules (LCXZ) sensitize ovarian cancer to cisplatin (DDP) treatment. METHODS: LC-MS analysis was used to identify the blood components of LCXZ after its administration in mice via gavage. In a BALB/c mouse model bearing subcutaneous ovarian cancer xenografts, the effects of daily gavage of distilled water (control group), intraperitoneal injection of DDP (5 mg/kg) once a week, or both DDP injection and daily LCXZK gavage (15 g/kg) on tumor growth were evaluated. Histopathological changes in the xenografts and kidneys were assessed with HE staining. RNA-seq was performed to identify the differentially expressed genes followed by KEGG pathway analysis. The changes in mitochondrial ultrastructure and expressions of mitochondrial apoptosis-related were examined with transmission electron microscopy and Western blotting. RESULTS: A total of 218 blood-borne components of LCXZ were detected by LC-MS. In the tumor-bearing mice, treatments with DDP and DDP combined with LCXZ redcued the tumor volume by 60.3% and 72.6% compared with that in the control group, respectively. Transcriptomic analysis revealed significantly upregulated ANT3 expression in both the two treatment groups. Molecular docking indicated that the main active components of LCXZ were capable of binding to adenine nucleotide translocator 3 (ANT3) with binding energies below -6 kcal/mol. Transmission electron microscopy showed obvious mitochondrial swelling and outer-membrane damage in the tumor cells in DDP-treated mice, and these changes were more pronounced in the combined treatment group. The expression levels of BAX, ANT3, cleaved caspase-3 and cleaved caspase-9 were increased, whereas BCL-2 expression was decreased significantly in the tumor cells in both the DDP and DDP+LCXZ groups. CONCLUSIONS LCXZ enhances the therapeutic efficacy of cisplatin against ovarian cancer xenografts in mice by promoting mitochondrial dysfunction and activating apoptotic signaling pathways via upregulating ANT3.
Animals ; Female ; Cisplatin/pharmacology* ; Ovarian Neoplasms/metabolism* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Mice, Inbred BALB C ; Mice ; Rats ; Xenograft Model Antitumor Assays ; Humans ; Cell Line, Tumor ; Antineoplastic Agents/pharmacology*

Objective To investigate the molecular mechanism by which Lichong Xiaozheng Granules(LCXZ)sensitize ovarian cancer to cisplatin(DDP)treatment.Methods LC-MS analysis was used to identify the blood components of LCXZ after its administration in mice via gavage.In a BALB/c mouse model bearing subcutaneous ovarian cancer xenografts,the effects of daily gavage of distilled water(control group),intraperitoneal injection of DDP(5 mg/kg)once a week,or both DDP injection and daily LCXZK gavage(15 g/kg)on tumor growth were evaluated.Histopathological changes in the xenografts and kidneys were assessed with HE staining.RNA-seq was performed to identify the differentially expressed genes followed by KEGG pathway analysis.The changes in mitochondrial ultrastructure and expressions of mitochondrial apoptosis-related were examined with transmission electron microscopy and Western blotting.Results A total of 218 blood-borne components of LCXZ were detected by LC-MS.In the tumor-bearing mice,treatments with DDP and DDP combined with LCXZ redcued the tumor volume by 60.3%and 72.6%compared with that in the control group,respectively.Transcriptomic analysis revealed significantly upregulated ANT3 expression in both the two treatment groups.Molecular docking indicated that the main active components of LCXZ were capable of binding to adenine nucleotide translocator 3(ANT3)with binding energies below-6 kcal/mol.Transmission electron microscopy showed obvious mitochondrial swelling and outer-membrane damage in the tumor cells in DDP-treated mice,and these changes were more pronounced in the combined treatment group.The expression levels of BAX,ANT3,cleaved caspase-3 and cleaved caspase-9 were increased,whereas BCL-2 expression was decreased significantly in the tumor cells in both the DDP and DDP+LCXZ groups.Conclusion LCXZ enhances the therapeutic efficacy of cisplatin against ovarian cancer xenografts in mice by promoting mitochondrial dysfunction and activating apoptotic signaling pathways via upregulating ANT3.

Objective To provide scientific evidence for studying biological characteristic of cockroaches and control countermeasures by investigating the species distribution and inroads situation of cockroaches in civil aircraft.Methods In August 2015,the onsite investigations were done for 19 A320 and A321 aircrafts harbored at Sanya airport and Haikou airport for getting the cockroach density.The difference of cockroache density was compared by aircraft type,aircraft age and the 4 areas of the aircraft.Results The total invasion rate was 84.21％ on 19 aircrafts.Blauella germanica is the dominant specie.The invasion rates of cockroaches was not statistically significant neither by the comparison of aircraft type (x2 =1.362,P＞0.05) nor by the comparison of aircraft age (x2=0.281,P ＞ 0.05).But statistical significance on cockroaches density was found in the comparison of 4 areas of aircrafts (x2=14.629,P＜0.01).Conclusions The comprehensive countermeasures,including environmental,physical and chemical controls,should be adopted according to the aircraft structure,operation and safety requirements.

Objective To provide scientific evidence for studying biological characteristic of cockroaches and control countermeasures by investigating the species distribution and inroads situation of cockroaches in civil aircraft.Methods In August 2015,the onsite investigations were done for 19 A320 and A321 aircrafts harbored at Sanya airport and Haikou airport for getting the cockroach density.The difference of cockroache density was compared by aircraft type,aircraft age and the 4 areas of the aircraft.Results The total invasion rate was 84.21％ on 19 aircrafts.Blauella germanica is the dominant specie.The invasion rates of cockroaches was not statistically significant neither by the comparison of aircraft type (x2 =1.362,P＞0.05) nor by the comparison of aircraft age (x2=0.281,P ＞ 0.05).But statistical significance on cockroaches density was found in the comparison of 4 areas of aircrafts (x2=14.629,P＜0.01).Conclusions The comprehensive countermeasures,including environmental,physical and chemical controls,should be adopted according to the aircraft structure,operation and safety requirements.