OBJECTIVE:To elucidate the potential molecular mechanism by which Fuzheng Kang’ai decoction(扶正抗癌方,FZKA)inhibits proliferation,migration,and invasion of lung cancer cells.METHODS:Varying FZKA concentrations were ...OBJECTIVE:To elucidate the potential molecular mechanism by which Fuzheng Kang’ai decoction(扶正抗癌方,FZKA)inhibits proliferation,migration,and invasion of lung cancer cells.METHODS:Varying FZKA concentrations were used to manage lung cancer cells(A549 and PC9).We employed:cell counting kit-8(CCK-8)and plate clone formation assays to examine the cell viability;flow cytometry(FCM)to analyze the cycle arrest;transwell and woundhealing assays to assess the cell invasion and migration,respectively.Further,a quantitative real-time polymerase chain reaction(q RT-PCR)assay was adopted to evaluate the miR-21-5p expression.For protein expression analysis,we employed the Western blot technique.Recombinant miR-21-5p overexpression adenovirus vector harboring GFP was constructed and transfected into A549 and PC9,after which we explored the effect of FZKA on miR-21-5p overexpression.RESULTS:Notably,treatment with FZKA inhibited viability,clone-formation ability,invasion,and migration of lung cancer cells.Mechanistically,FZKA markedly suppressed miR-21-5p expression but elevated the human phosphatase and tensin homology deleted on chromosome ten(PTEN)protein level in both A549 and PC9 cells.Over-expression of miR-21-5p lowered PTEN protein expression.Besides,overexpressed miR-21-5p levels with adenovirus antagonized FZKA-upregulated PTEN protein expression.CONCLUSION:The present study demonstrates how FZKA modulates cell biological behaviors,for instance,it impedes the proliferation by upregulating PTEN expression with miR-21-5p as the target.These findings unveil the potential novel molecular mechanisms from the micro RNA aspect by which FZKA suppresses the growth of human lung cancer cells.展开更多
Objective： To evaluate the effect of Fuzheng Kang＇ai Formula （扶正抗癌方, FZKA） plus gefitinib in patients with advanced non-small cell lung cancer with epidermal growth factor receptor （EGFR） mutations. Methods...Objective： To evaluate the effect of Fuzheng Kang＇ai Formula （扶正抗癌方, FZKA） plus gefitinib in patients with advanced non-small cell lung cancer with epidermal growth factor receptor （EGFR） mutations. Methods： A randomized controlled trial was conducted from 2009 to 2012 in South China. Seventy chemotherapynaive patients diagnosed with stage ⅢB/Ⅳ non-small cell lung cancer with EGFR mutations were randomly assigned to GF group [gefitinib （250 mg/day orally） plus FZKA （250 mL, twice per day, orally）; 35 cases] or G group （gefitinib 250 mg/day orally; 35 cases） according to the random number table and received treatment until progression of the disease, or development of unacceptable toxicities. The primary endpoint [progression-free survival （PFS）] and secondary endpoints [median survival time （MST）, objective response rate （ORR）, disease control rate （DCR） and safety] were observed. Results： No patient was excluded after randomization. GF group had significantly longer PFS and MST compared with the G group, with median PFS of 12.5 months （95% CI 3.30-21.69） vs. 8.4 months （95% CI 6.30-10.50; log-rank P〈0.01）, MST of 21.5 months （95% CI 17.28-25.73） vs. 18.3 months （95% CI 17.97-18.63; log-rank P〈0.01）. ORR and DCR in GF group and G group were 65.7% vs. 57.1%, 94.3% vs. 80.0%, respectively （P〉0.05）. The most common toxic effects in the GF group and G group were rash or acne （42.8% vs. 57.1%, P〉0.05）, diarrhea （11.5% vs. 31.4%, P〈0.05）, and stomatitis （2.9% vs. 8.7%, P〉0.05）. Conclusion： Patients with advanced non-small cell lung cancer selected by EGFR mutations have longer PFS, MST with less toxicity treated with gefitinib plus FZKA than gefitinib alone.展开更多
Objective:To study the mechanism of Chinese herbal medicine Fuzheng Kang’ai Formula(FZKA)on tumor microenvironment(TME).Methods:CIBERSORTx was used for analysis of TME.Traditional Chinese Medicine Systems Pharmacolog...Objective:To study the mechanism of Chinese herbal medicine Fuzheng Kang’ai Formula(FZKA)on tumor microenvironment(TME).Methods:CIBERSORTx was used for analysis of TME.Traditional Chinese Medicine Systems Pharmacology and Analysis Platform was applied to identify compounds-targets network and the Cancer Genome Atlas(TCGA)was employed to identify the differential expression genes(DEGs)between tumor and paracancerous tissues in lung adenocarcinoma(LUAD)from TCGA-LUAD.Additionally,DEGs with prognosis in LUAD was calculated by univariable and multivariate Cox regression.The core targets of FZKA were analyzed in lung adenocarcinoma TME.Protein-protein interaction database was employed to predict down-stream of target.Quantitative reverse transcription polymerase chain reaction was employed for biological experiment in A549,H1299 and PC9 cell lines.Results:The active and resting mast cells were significantly associated with prognosis of LUAD(P<0.05).Of the targets,CCNA2 as an important target of FZKA(hazard ratio=1.41,95%confidential interval:1.01-2.01,P<0.05)was a prognostic target and significantly associated with mast cells.CCNA2 was positively correlated with mast cell activation and negatively correlated with mast cell resting state.BCL1 L2,ACTL6 A and ITGAV were down-stream of CCNA2,which were validated by q RT-PCR in A549 cell.Conclusion:FZKA could directly bind to CCNA2 and inhibit tumor growth by regulating CCNA2 downstream genes and TME of NSCLC closely related to CCNA2.展开更多
Objective To observe the effect of Fuzheng Kang’ai Recipe(FKR)combined with gefitinib on the proliferation and apoptosis of lung cancer A549 cells,and to study its potential synergistic mechanish with gefitinib.Metho...Objective To observe the effect of Fuzheng Kang’ai Recipe(FKR)combined with gefitinib on the proliferation and apoptosis of lung cancer A549 cells,and to study its potential synergistic mechanish with gefitinib.Methods The effects of FKR(0.211,0.316,0.474,0.711,1.067,1.600,2.400,3.600 mg/mL)combined with展开更多
目的观察扶正抑癌方抗大肠癌肝转移的作用,并探讨其可能的作用机制。方法将40只BALB/C裸鼠随机分为5组:模型组、中药组、化疗组、防治组、联合组,以5×106个/m l浓度的LoVo细胞悬液0.2 m l接种于裸鼠脾脏,建立大肠癌肝转移模型。后...目的观察扶正抑癌方抗大肠癌肝转移的作用,并探讨其可能的作用机制。方法将40只BALB/C裸鼠随机分为5组:模型组、中药组、化疗组、防治组、联合组,以5×106个/m l浓度的LoVo细胞悬液0.2 m l接种于裸鼠脾脏,建立大肠癌肝转移模型。后4组分别予扶正抑癌方治疗、5-Fu治疗、扶正抑癌方防治、扶正抑癌方+5-Fu治疗,分别从移植瘤和转移瘤的重量、形态学以及血清癌胚抗原浓度来观察扶正抑癌方的疗效。结果与模型组相比,防治组、联合组、化疗组脾脏接种瘤、肝脏转移瘤重量均减轻(P<0.05),其中联合组低于化疗组(P<0.05);而且联合组、化疗组CEA含量明显降低(P<0.05)。中药组上述指标无显著差异(P>0.05)。结论扶正抑癌方联合5-Fu可以降低模型动物的肝转移发生率,抑制脾脏接种瘤、肝脏转移瘤的生长。展开更多
目的探讨扶正抗癌方联合化疗治疗晚期非小细胞肺癌(NSCLC)的疗效和安全性。方法在中国生物医学文献数据库、Pub Med等数据库检索扶正抗癌方联合化疗治疗晚期NSCLC的随机对照试验(RCT),采用Meta分析专用软件Rev Man 5.2进行系统评价。结...目的探讨扶正抗癌方联合化疗治疗晚期非小细胞肺癌(NSCLC)的疗效和安全性。方法在中国生物医学文献数据库、Pub Med等数据库检索扶正抗癌方联合化疗治疗晚期NSCLC的随机对照试验(RCT),采用Meta分析专用软件Rev Man 5.2进行系统评价。结果共纳入6个RCT,均为B级文献,共有467例NSCLC患者。Meta分析显示,扶正抗癌方联合化疗治疗晚期NSCLC的有效率优于单纯化疗组,差异有统计学意义[RR=1.87,95%CI(1.28~2.72)];扶正抗癌方联合化疗组的不良反应发生率低于单纯化疗组,差异有统计学意义[RR=0.29,95%CI(0.16~0.54)]。研究无明显发表偏倚。结论现有研究表明,扶正抗癌方联合化疗治疗晚期NSCLC的有效率优于单纯化疗组,且安全性更佳。展开更多
基金Supported by China Postdoctoral Science Foundation(No.2020M672745)the Research Project of Traditional Chinese Medicine Bureau of Guangdong Province(No.20201149,Ultrasound-delivery System to Deliver Solasonine to Regulate miR-141-3p and Enhance the Inhibition of Lung Cancer by Gefitinib)the National Natural Science Foundation of China of China(No.81503507:Exploring the Mechanism on Reversal of Gefitinib Resistance in Treating Non-Small Cell Lung Cancer by Fuzhengkangai Decoction base on miRNA-206/449a,81974543:Research on Fuzheng kang’ai Formula Reversing the Drug Resistance to Gefitinib in Non-Small Cell Lung Cancer(NSCLC)via inducing Ferroptosis by Regulating Ferritin and 81803919:the Molecular Mechanism of Fuzheng Kang-ai Decoction Reversing EMT based on Crosstalk between Tumor and Its Microenvironment)
文摘OBJECTIVE:To elucidate the potential molecular mechanism by which Fuzheng Kang’ai decoction(扶正抗癌方,FZKA)inhibits proliferation,migration,and invasion of lung cancer cells.METHODS:Varying FZKA concentrations were used to manage lung cancer cells(A549 and PC9).We employed:cell counting kit-8(CCK-8)and plate clone formation assays to examine the cell viability;flow cytometry(FCM)to analyze the cycle arrest;transwell and woundhealing assays to assess the cell invasion and migration,respectively.Further,a quantitative real-time polymerase chain reaction(q RT-PCR)assay was adopted to evaluate the miR-21-5p expression.For protein expression analysis,we employed the Western blot technique.Recombinant miR-21-5p overexpression adenovirus vector harboring GFP was constructed and transfected into A549 and PC9,after which we explored the effect of FZKA on miR-21-5p overexpression.RESULTS:Notably,treatment with FZKA inhibited viability,clone-formation ability,invasion,and migration of lung cancer cells.Mechanistically,FZKA markedly suppressed miR-21-5p expression but elevated the human phosphatase and tensin homology deleted on chromosome ten(PTEN)protein level in both A549 and PC9 cells.Over-expression of miR-21-5p lowered PTEN protein expression.Besides,overexpressed miR-21-5p levels with adenovirus antagonized FZKA-upregulated PTEN protein expression.CONCLUSION:The present study demonstrates how FZKA modulates cell biological behaviors,for instance,it impedes the proliferation by upregulating PTEN expression with miR-21-5p as the target.These findings unveil the potential novel molecular mechanisms from the micro RNA aspect by which FZKA suppresses the growth of human lung cancer cells.
基金Supported by the National Natural Science Foundation of China(No.81273965,81503507)the Natural Science Foundation of Guangdong Province(No.2015A030310245)
文摘Objective： To evaluate the effect of Fuzheng Kang＇ai Formula （扶正抗癌方, FZKA） plus gefitinib in patients with advanced non-small cell lung cancer with epidermal growth factor receptor （EGFR） mutations. Methods： A randomized controlled trial was conducted from 2009 to 2012 in South China. Seventy chemotherapynaive patients diagnosed with stage ⅢB/Ⅳ non-small cell lung cancer with EGFR mutations were randomly assigned to GF group [gefitinib （250 mg/day orally） plus FZKA （250 mL, twice per day, orally）; 35 cases] or G group （gefitinib 250 mg/day orally; 35 cases） according to the random number table and received treatment until progression of the disease, or development of unacceptable toxicities. The primary endpoint [progression-free survival （PFS）] and secondary endpoints [median survival time （MST）, objective response rate （ORR）, disease control rate （DCR） and safety] were observed. Results： No patient was excluded after randomization. GF group had significantly longer PFS and MST compared with the G group, with median PFS of 12.5 months （95% CI 3.30-21.69） vs. 8.4 months （95% CI 6.30-10.50; log-rank P〈0.01）, MST of 21.5 months （95% CI 17.28-25.73） vs. 18.3 months （95% CI 17.97-18.63; log-rank P〈0.01）. ORR and DCR in GF group and G group were 65.7% vs. 57.1%, 94.3% vs. 80.0%, respectively （P〉0.05）. The most common toxic effects in the GF group and G group were rash or acne （42.8% vs. 57.1%, P〉0.05）, diarrhea （11.5% vs. 31.4%, P〈0.05）, and stomatitis （2.9% vs. 8.7%, P〉0.05）. Conclusion： Patients with advanced non-small cell lung cancer selected by EGFR mutations have longer PFS, MST with less toxicity treated with gefitinib plus FZKA than gefitinib alone.
基金Supported by the Special Funds of Science and Technology Development of the Chinese Central Government to Guide Local in 2020(No.21JR1RA066,20JR10FA667)Hospital Fund of the First Hospital of Lanzhou University(No.ldyyyn2007-03)。
文摘Objective:To study the mechanism of Chinese herbal medicine Fuzheng Kang’ai Formula(FZKA)on tumor microenvironment(TME).Methods:CIBERSORTx was used for analysis of TME.Traditional Chinese Medicine Systems Pharmacology and Analysis Platform was applied to identify compounds-targets network and the Cancer Genome Atlas(TCGA)was employed to identify the differential expression genes(DEGs)between tumor and paracancerous tissues in lung adenocarcinoma(LUAD)from TCGA-LUAD.Additionally,DEGs with prognosis in LUAD was calculated by univariable and multivariate Cox regression.The core targets of FZKA were analyzed in lung adenocarcinoma TME.Protein-protein interaction database was employed to predict down-stream of target.Quantitative reverse transcription polymerase chain reaction was employed for biological experiment in A549,H1299 and PC9 cell lines.Results:The active and resting mast cells were significantly associated with prognosis of LUAD(P<0.05).Of the targets,CCNA2 as an important target of FZKA(hazard ratio=1.41,95%confidential interval:1.01-2.01,P<0.05)was a prognostic target and significantly associated with mast cells.CCNA2 was positively correlated with mast cell activation and negatively correlated with mast cell resting state.BCL1 L2,ACTL6 A and ITGAV were down-stream of CCNA2,which were validated by q RT-PCR in A549 cell.Conclusion:FZKA could directly bind to CCNA2 and inhibit tumor growth by regulating CCNA2 downstream genes and TME of NSCLC closely related to CCNA2.
文摘Objective To observe the effect of Fuzheng Kang’ai Recipe(FKR)combined with gefitinib on the proliferation and apoptosis of lung cancer A549 cells,and to study its potential synergistic mechanish with gefitinib.Methods The effects of FKR(0.211,0.316,0.474,0.711,1.067,1.600,2.400,3.600 mg/mL)combined with
文摘目的观察扶正抑癌方抗大肠癌肝转移的作用,并探讨其可能的作用机制。方法将40只BALB/C裸鼠随机分为5组:模型组、中药组、化疗组、防治组、联合组,以5×106个/m l浓度的LoVo细胞悬液0.2 m l接种于裸鼠脾脏,建立大肠癌肝转移模型。后4组分别予扶正抑癌方治疗、5-Fu治疗、扶正抑癌方防治、扶正抑癌方+5-Fu治疗,分别从移植瘤和转移瘤的重量、形态学以及血清癌胚抗原浓度来观察扶正抑癌方的疗效。结果与模型组相比,防治组、联合组、化疗组脾脏接种瘤、肝脏转移瘤重量均减轻(P<0.05),其中联合组低于化疗组(P<0.05);而且联合组、化疗组CEA含量明显降低(P<0.05)。中药组上述指标无显著差异(P>0.05)。结论扶正抑癌方联合5-Fu可以降低模型动物的肝转移发生率,抑制脾脏接种瘤、肝脏转移瘤的生长。
文摘目的探讨扶正抗癌方联合化疗治疗晚期非小细胞肺癌(NSCLC)的疗效和安全性。方法在中国生物医学文献数据库、Pub Med等数据库检索扶正抗癌方联合化疗治疗晚期NSCLC的随机对照试验(RCT),采用Meta分析专用软件Rev Man 5.2进行系统评价。结果共纳入6个RCT,均为B级文献,共有467例NSCLC患者。Meta分析显示,扶正抗癌方联合化疗治疗晚期NSCLC的有效率优于单纯化疗组,差异有统计学意义[RR=1.87,95%CI(1.28~2.72)];扶正抗癌方联合化疗组的不良反应发生率低于单纯化疗组,差异有统计学意义[RR=0.29,95%CI(0.16~0.54)]。研究无明显发表偏倚。结论现有研究表明,扶正抗癌方联合化疗治疗晚期NSCLC的有效率优于单纯化疗组,且安全性更佳。
