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The disease spectrum of ABCB4 gene mutation involves various diseases such as progressive familial intrahepatic cholestasis type 3 （PFIC3）， gallstone disease， intrahepatic cholestasis of pregnancy， portal hypertension， liver cirrhosis， and even primary hepatic and biliary malignancies. A young male patient was admitted to Department of Hepatobiliary Medicine， Eastern Hepatobiliary Surgery Hospital， and was initially diagnosed with liver cirrhosis and gallstones， and he was planned to receive laparoscopic cholecystectomy. Preoperative examination showed abnormal liver function， liver cirrhosis， splenomegaly， and mild esophageal varices， and next-generation sequencing was performed to make a confirmed diagnosis of ABCB4 gene mutation-associated liver cirrhosis with gallstones. The liver function of the patient gradually returned to normal after cholagogic treatment with ursodeoxycholic acid capsules.
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Aims: To investigate the differences and international connections between the human cervical cancer cell line (HeLa cells) and the Taxol-resistant HeLa cell line (HeLa/Taxol). Materials and Methods: As parental cells, HeLa cells were cultured in stepwise escalating concentration of Taxol from 0.01 μg/ml (11.7 × 10−9 mol/L) to 0.5 μg/ml (585 × 10−9 mol/L). The drug resistance of HeLa/Taxol cells was detected by methyl-thiazolyl-tetrazolium assay. Real time-polymerase chain reaction (RT-PCR) was conducted to detect the messenger RNA levels of drug resistance genes and apoptosis-related genes. The proteins levels were detected through immunofluorescence and Western blot. Results: Compared with parental HeLa cells, HeLa/Taxol with Taxol resistance had the following biological characteristics: first, they had a lower growth velocity; second, the expression of P-glycoprotein and glutathione S-transferases was significantly increased; Third, the expression of antiapoptotic protein Bcl-2 and apoptosis inhibitor protein survivin was prominently increased. Conclusions: The drug-resistance in HeLa/Taxol is mainly associated with the high expression of multidrug resistance genes, antiapoptotic protein Bcl-2, and apoptosis inhibitor protein survivin as an important reason for the failure of chemotherapy of tumor tissue
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Objective: To investigate the effects of stromal cell-derived factor-1α (SDF-1α)through CXC-domain chemokine receptor 4 (CXCR4) and CXCR7 on colonic cancer cells resistant to 5-fluorouracil (5-FU), and to explore its possible mechanism. Methods: The expression levels of CXCR4 and CXCR7 in colonic cancer SW480, SW620, HCT116 and HT29 cells were detected by Western blotting. After treatment with SDF-1α, SDF-1α in combination with AMD3100 (CXCR4 inhibitor) or SDF-1α in combination with anti-CXCR7 monoclonal antibody for 6 hours, the SW480 and HT29 cells were then treated with 3.1, 6.25, 12.5, 25, 50, 100 and 150 μg/mL 5-FU for 48 hours. The half inhibitory concentration (IC50) value of 5-FU was detected by sulforhodamine B (SRB) assay. The expressions of drug-resistant proteins P-glycoprotein (P-gp) and multidrug resistance protein-1 (MRP-1) were detected by Western blotting. Results: The expression levels of CXCR4 and CXCR7 in SW480 and HT29 cells were higher than those in SW620 and HCT116 cells (all P 0.05). The expression levels of P-gp in SW480 and HT29 cells in group of SDF-1α in combination with anti-CXCR7 monoclonal antibody were lower than those in SDF-1α group (both P 0.05). The expression level of MRP-1 had no significant difference among different groups (P > 0.05). Conclusion: SDF-1α can promote the resistance to 5-FU in colonic cancer cells. This effect may be related to up-regulating the expression level of P-gp through SDF-1α/CXCR7 signal pathway.
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Objective To investigate the role of the ATP binding box C subfamily 2 transporter protein (ABCC2) gene in drug-resistant epilepsy.Methods From February 2014 to February 2018,204 epileptic patients were treated in our hospital,including 41 cases of drug resistance epilepsy (drug resistance group),163 cases of non drug resistant epilepsy (sensitive group).The rs717620 polymorphism of ABCC2 gene and the level of P-glycoprotein (P-gp) in cerebrospinal fluid and serum were detected in two groups.Results The proportion of genotype TT and gene frequency T in the drug resistant group were 24.39％ and 41.46％,respectively,which were significantly higher than those in the sensitive group (P ＜ 0.05).The concentration of P-gp in cerebrospinal fluid of drug resistant group was (21.03 ± 4.21) ng/ml,which was significantly higher than that of the sensitive group (P ＜ 0.05).There was no significant difference in serum P-gp concentration between the drug resistant group and the sensitive group (P ＞ 0.05);The concentration of P-gp in cerebrospinal fluid of patients with genotype TT in drug resistance group was (24.03 ± 3.57) ng/ml,which was significantly higher than that of type CC and CT (P ＜ 0.05).There was no significant difference in the concentration of P-gp in the patients with different genotypes in the drug resistant group (P ＞ 0.05).Conclusions The rs717620 polymorphism of ABCC2 gene may be associated with drug-resistant epilepsy,and may be related to P-gp level in the cerebrospinal fluid.
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Objective: To investigate the effect of solanine on multidrug resistance of leukemia K562/ADR cells, and to explore its mechanism. Methods: K562/ADR cells were treated with different concentrations (5-40 μg/mL) of solanine alone or in combination with doxorubicin (DOX) for 24 h. The intracellular toxicity and DOX-sensitization effect of solanine were detected by CCK-8 assay. The cell-associated mean fluorescence intensity of DOX was detected by FCM method. The expressions of multidrug resistance-associated protein 1 (MRP1), c-Jun NH2-terminal kinase (JNK), and phosphorylated JNK (p-JNK) were determined by Western blotting. Results: Solanine at non-toxic doses (5 and 10 μg/mL) significantly enhanced the cytotoxicity of DOX (both P < 0.05), and significantly increased the mean fluorescence intensity of DOX in K562/ADR cells in a dose-dependent manner (both P < 0.05). After treatment with 5 and 10 μg/mL solanine, the expression levels of MRP1 and p-JNK proteins were significantly decreased (all P < 0.05) in K562/ADR cells. Conclusion: Solanine can reverse multidrug resistance of K562/ADR cells in vitro. The mechanism may be related to blocking JNK signaling pathway and downregulating MRP1 expression.
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Objective@#To investigate the relationship between expression of FoxM1 and BCRP in invasive breast carcinoma of no special type (IBC-NST) tissues and the clinical pathological characteristics and prognosis of the patients.@*Methods@#Seventy-eight cases of IBC-NST with excision were included. The expression of FoxM1 and BCRP was assessed by immunohistochemistry and its relationship with the clinical pathological characteristics and prognosis was evaluated.@*Results@#FoxM1 was expressed in 71.8%(56/78) of IBC-NST, and the expression was related to tumor diameter, TNM staging, ER, PR and HER2. BCRP was expressed in 53.8% (42/78) of IBC-NST, and the expression was related to age, tumor diameter, lymph node metastasis, ER and HER2. Kaplan-Meier survival analysis showed the survival time was related to tumor diameter, TNM staging, lymph node metastasis and the expression of FoxM1, BCRP, ER, PR and HER2. Cox multivariate analysis showed that TNM staging, FoxM1, BCRP, HER2 were determinants of patient survival time.@*Conclusions@#The expression of FoxM1 is associated with tumor diameter, TNM staging, ER, PR and HER2 while BCRP is associated with age, tumor diameter, lymph node metastasis, ER and HER2. Both FoxM1 and BCRP have prognostic significance in IBC-NST patients.
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Objective To study the effect of enhanced MK gene expression in hepatic carcinoma cells.Methods The recombinant plasmid pIRES2-EGFP-MK was transfected into SMMC 7721 cells.The mRNA and protein expression levels of MK gene in these cells were determined by real-time PCR,Western blotting and flow cytometry.The intracellular DNR accumulation of these cells was measured by flow cytometry.To investigate the effect of MK gene mediated multidrug resistance,MTT assay was employed to determine the cellular sensitivity of different chemotherapeutic drugs in MK-overexpressed SMMC 7721 cells.Results The mRNA and protein expression levels of MK gene significantly increased after the recombinant plasmid pIRES2-EGFP-MK transfected into SMMC 7721 cells,suggesting that the recombinant plasmid pIRES2-EGFP-MK can enhance the transcription of MK effectively.The DNR accumulation of MK transfected cells decreased significantly (4.06 ± 0.88,P ＜ 0.05),and IC50 of MK transfected cells to ADM/5-FU increased significantly (15 ± 3,27 ± 4,P ＜ 0.05).Conclusions After the recombinant plasmid pIRES2-EGFP-MK transfected into hepatic carcinoma cells,expression of midkine increased,enhancing the resistance of hepatic carcinoma cells to chemotherapeutic drugs.
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Objective To observe the effect of magnesium isoglycyrrhizinate on the expressions of UGT1A, MRP2 protein and mRNA of L-02 cells damaged by triptolide, and to investigate hepatoprotective mechanism of magnesium isoglycyrrhizinate in terms of drug metabolism. Methods L-02 cells were divided into 4 groups:normal group, triptolide group, magnesium isoglycyrrhizinate group and rifampicin group. Magnesium isoglycyrrhizinate group and rifampicin group were pretreated by magnesium isoglycyrrhizinate and rifampicin for 24 h and the remaining two groups added medium. Triptolide were added for 18 h except normal group. Cell survival rate was tested by MTT. The expression levels of UGT1A, MRP2 protein and mRNA were detected by Western blot assay and RT-PCR. Results Compared with triptolide group, cell survival rate was significantly higher in magnesium isoglycyrrhizinate group (P<0.05). Meanwhile, the expression levels of UGT1A, MRP2 protein and mRNA were significantly lower in triptolide group compared with those of control group (P<0.05). The expression levels of UGT1A, MRP2 protein and mRNA were significantly up-regulated in magnesium isoglycyrrhizinate pretreatment group than those of triptolide group (P<0.05). The UGT1A protein and mRNA expressions were significantly decreased in rifampicin pretreatment group than those of magnesium isoglycyrrhizinate group ( P<0.05), but there were no significant differences in MRP2 protein and mRNA expressions between the two groups. Conclusion Magnesium isoglycyrrhizinate shows protective effects on triptolide induced L-02 cell injury, which may be involved with the activation of UGT1A and MRP2.
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Objective To investigate the expression and relationship between hepatocyte cell adhesion molecule (hepaCAM) protein and some multidrug resistance proteins in renal carcinoma tissue.Methods Expressions of hepaCAM,multidrug resistance associated protein (MRP),P-glycoprotein (P-gp),lung resistance protein (LRP),and topoisomerase Ⅱ (TOPO Ⅱ) protein were detected by immunohistochemistry in different areas of human renal cell carcinoma tissues and their relationships were analyzed.Results In the peripheral zone of renal tumor,hepaCAM,MRP,P-gp and LRP protein were showed positive expression.In the central region of the renal tumor,the expressions of hepaCAM,P-gp and LRP were negative or weakly positive,while the expressions of MRP and TOPO Ⅱ protein were positive.The expressions of MRP and TOPO Ⅱ protein in the central region of tumor were stronger than those in the peripheral zone of tunor (31.23 ±5.67 vs.23.89 ±4.56;45.66 ±2.34 vs.5.23 ±0.66),with statistically significant differences (t =-6.20,P =0.00;t =-100.16,P =0.00).While the expressions of other proteins (hepaCAM,P-gp and LRP) in the central region of tumor were weaker than those in the peripheral zone of tumor (3.21 ±1.12 vs.27.25±2.23;2.34±0.33 vs.51.23±3.45;4.22±1.78 vs.44.23 ± 1.45),with statistically significant differences (t =60.87,P =0.00;t =90.35,P =0.00;t =107.18,P =0.00).Correlation analysis showed that the expression of hepaCAM protein in the central region of renal carcinoma was related with the expression of MRP protein (r =0.94,P =0.01),but it was not related with the expressions of P-gp,LRP and TOPO Ⅱ protein (r=0.22,P=0.44;r=0.14,P=0.80;r=0.34,P=0.07).Conclusion The expression of hepaCAM protein in renal carcinoma may be related to tumor drug-resistance.
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The indication for eradication of Helicobacter pylori( Hp)has been gradually expanded from peptic ulcer to“confirmed Hp infection”. Kyoto global consensus report on Hp gastritis has defined Hp gastritis as an infectious disease, and proposed that eradication therapy should be given to Hp infected individuals unless there are competing considerations. Currently the issue of Hp infection is no longer whether it should be eradicated,but rather how it can be effectively eradicated. With the rise of antibiotic resistance,Hp eradication is much more difficult than beforehand. This series of lectures on how to improve the eradication rate of Hp has been elaborated in detail in following aspects:current status of Hp eradication therapy,how to improve the eradication rate of drug-resistant strains of Hp,and to explore suitable eradication regimens for Chinese patients in reference with international consensus.
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Objective: To investigate the reversal effect of blocking phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signal pathway on hydroxycampothecin (HCPT)-resistance of colorectal cancer SW1116/HCPT cells. Methods: The expression levels of Akt and phospho-Akt (p-Akt) in the parent cell line SW1116 and HCPT-resistant cell line SW1116/HCPT were detected by Western blotting. The specific inhibitor LY294002 and siRNA targeting Akt gene were used to block the expression of Akt. Then the proliferation of SW1116/HCPT cells was detected by MTT assay. The expression levels of ATP-binding cassette transporter G2 (ABCG2) mRNA and protein were detected by real-time fluorescent quantitative PCR and Western blotting, respectively. The drug-efflux function was detected by Rhodamine 123 (Rh123) method. Results: The expression level of p-Akt in SW1116/HCPT cells was higher than that in parent SW1116 cells (P < 0.01). LY294002 and Akt-siRNA could inhibit the expression level of p-Akt, suppress the proliferation of SW1116/HCPT cells, and increase the sensitivity to HCPT (all P < 0.01). LY294002 could down-regulate the expressions of ABCG2 mRNA and protein by (74.82±4.71)% and (58.24±4.78)% (both P < 0.01), respectively. The accumulation of Rh123 in SW1116/HCPT cells was increased 1.45±0.12 times 48 h after treatment (P < 0.01). After silencing the expression of Akt, the expressions of ABCG2 mRNA and protein were decreased by (59.63±5.14)% and (44.41±2.56)% (both P < 0.01), respectively, and the concentration of intracellular Rh123 was increased 1.22±0.10 times (P < 0.01). Conclusion: PI3K/Akt signal pathway can up-regulate the expression of drug-resistance gene ABCG 2, and play a vital role in the carcinogenesis of multidrug-resistance induced by HCPT.
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Objective: To investigate the reversal effect of curcumin (Cur) on multidrug resistance of human esophageal cancer vincristine (VCR)- resistant Eca-109/VCR cells, and to explore its possible mechanism. Methods: The effects of different concentrations of VCR on the proliferation of parental Eca-109 cells and VCR-resistant Eca-109/VCR cells, as well as the reversal effect of Cur combined with VCR on multidrug resistance of Eca-109/VCR cells were detected by CCK-8 method. The apoptosis rates of Eca-109/VCR cells after treatment with Cur (20 μmol/L) combined with VCR (2 μg/mL) for 6, 12 or 24 h were detected by FCM. The expression level of multiple drug resistance 1 (MDR1) mRNA in Eca-109/VCR cells was measured by real-time fluorescent quantitative PCR. The expression levels of P-glycoprotein (P-gp) and multidrug resistance-related protein (MRP) were detected by immunocytochemistry. Results: The proliferation inhibitory rates of Eca-109/VCR cells were (8.08±0.23)% after treatment with 20 μmol/L Cur for 24 h. The half inhibitory concentration (IC50) of VCR was 0.157 and 2.524 μg/mL in Eca-109 cells and Eca-109/VCR cells, respectively. After treatment with Cur (20 μmol/L) combined with various concentrations of VCR, the drugresistant reversal fold was 3.58 in Eca-109/VCR cells. After treatment with Cur (20 μmol/L) combined with VCR (2 μg/mL) for 12 and 24 h, the apoptosis rates of Eca-109/VCR cells were (11.27±0.21)% and (18.77±0.26)%, which were higher than that in VCR (2 μg/mL) group (both P<0.05). After treatment with Cur (20 μmol/L) combined with VCR (2 or 3 μg/mL) for 24 h, the expression level of MDR1 mRNA in Eca-109/VCR cells was significantly reduced (both P<0.05), and the expression levels of P-gp and MRP were significantly decreased as compared with VCR (2 μg/mL) treatment group (all P<0.05). Conclusion: Cur can reverse multidrug resistance of esophageal cancer Eca-109/VCR cells, and its mechanism may be related to the down-regulation of P-gp and MRP expressions.
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Chemotherapy is one of the main treatment methods in malignant tumor.Tumor multidrug resistance (MDR) is one of the important reasons for the failure of chemotherapy.It makes some progress in reversing tumor MDR,such as chemical drug,traditional Chinese medicine,immunotherapy,gene therapy,nanoparticles drug system and so on.But it takes more effort to develop medicine of less adverse reactions,better pharmacodynamic and application to clinic widely.
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Hepatocellular carcinoma (HCC)is one of the most common malignant tumors in China,with a very complex mechanism of de-velopment and progression.Clusterin (CLU)has been confirmed to play an important role in the development and progression of HCC.This paper reviews the molecular structure and biological function of CLU and its value for early diagnosis of HCC and analyzes its association with multi -drug resistance in chemotherapy and the prospect of targeted therapy.CLU holds promise as a new molecular marker of HCC and the therapeutic target.
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Objective: To investigate the impact of low-dose metronomic chemotherapy (LDM) and maximum tolerated dose chemotherapy (MTD) with cisplatin on BALB/c nude mice bearing human ovarian cancer and the xenograft tumors of SKOV3 cells, and to explore the influence of these two chemotherapeutic protocols on expression levels of breast cancer resistant protein (BCRP), lung resistance protein (LRP) and tumor stem cell marker CD133. Methods: The human ovarian cancer SKOV3 cells were used to establish BALB/c nude mice model bearing subcutaneous tumor xenografts. Thirty-six mice were randomly divided into three groups: control group (n = 12), LDM group (n = 12) and MTD group (n = 12). The general situation of nude mice and the growth of tumor xenografts were observed during chemotherapy, and the tumor inhibition rate was calculated. The expression levels of BCRP, LRP and CD133 proteins in tumor xenografts in nude mice were detected by Western blotting. The small metastatic lesions in internal organs and the pathological feature of tumor xenografts were observed by hematoxylin-eosin (HE) staining. Results: The volume of tumor xenografts of MTD and LDM groups were significantly smaller than that of the control group (P < 0.05), while the tumor volume of LDM group was significantly smaller than that of MTD group. The tumor inhibition rates of MTD group and LDM group were 27.00% and 54.29%, respectively. The body weight and food-intake of mice in MTD group and LDM group were both significantly lower than those in the control group (all P < 0.05). As compared to LDM group and the control group, white blood cell (WBC) count in MTD group was lower (P < 0.05). Hepatocellular fatty degeneration was observed in two mice in MTD group. The expression levels of BCRP, LRP and CD133 proteins in tumor xenografts in MTD group and LDM group were significantly higher than those in the control group (all P < 0.05), while the BCRP and CD133 protein expression levels in LDM group were lower than those in MTD group. Conclusion: LDM can lead to greater tumor growth inhibition and less bone marrow suppression as compared with MTD, at the same total cumulative dose. Tumor cells with partial tumor stem cell properties and high expression levels of drug resistance-related proteins were easier to be enriched in MTD model. LDM is a new potential therapeutic mode which may reduce tumor recurrence and increase the sensitivity to chemotherapy.
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In recent years, direct-acting antiviral agent(DAA) that target specific enzymes in the life cycle of hepatitis C virus (HCV) have been developed rapidly. However, there are specific resistance-related mutation sites for DAA, which is associated with the gene types/subtypes of HCV. This article describes the resistance-related mutation sites for DAA and their impacts on the treatment regimen according to the mechanism of action of DAA. It is pointed out that some natural mutation sites lead to drug resistance in the treatment for patients with some HCV subtypes, so careful evaluation is needed before treatment to determine the appropriate regimen. For patients experiencing failure in the previous interferon therapy, the pre-existing drug resistance should be studied if DAA in combination with the therapy or interferon-free DAA therapies are to be used.
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Objective To investigate the association between single nucleotide polymorphisms (SNPs) of ATP-binding cassette B1 (ABCB1),ATP-binding cassette C2 (ABCC2) and solute carrier organic anion transporter 1B1 (SLCO1 B1) genes with high dose methotrexate (HDMTX)-induced toxicity in children with acute lymphoblastic leukemia (ALL).Methods This study was designed as a casecontrol.From September of 2005 to December of 2011,the blood samples were randomly collected from 142ALL patients from Nanjing Children's Hospital,Enzyme-multiplied immunoassay technique (EMIT) was used to measure the plasma concentration of MTX,Seven SNPs in ABCB1 (rs1045642,rs2032582,rs1128503),ABCC2 (rs717620,rs2273697) and SLCO1 B1 (rs4149081,rs11045879) genes were detected by polymerase chain reaction-ligase detection reaction (PCR-LDR).Results A significantly increased risk of MTX-induced toxicity was observed in patients with MTX elimination delay (OR ＝ 2.828,95％ CI:1.217-6.571,P ＜ 0.05).Two SNPs in SLCO1B1,rs4149081 and rs11045879 were linkage disequilibrium (LD) with each other (R2 =0.979,P ＜ 0.05).Multivariate analysis revealed that individuals with SLCO1B1 rs4149081 AA genotype or SLCO1B1 rs11045879 CC genotype showed increased incidence of MTX elimination delay (OR =4.41,95％ CI:1.537-12.654,P =0.042),and the two genotypes were also associated with significantly increased risk of MTX-induced toxicity (OR =4.118,95％ CI:1.135-14.944,P =0.022).No association of MTX elimination delay or MTX-induced toxicity with the other SNPs analyzed was found.Conclusions SLCO1B1 rs4149081 AA or SLCO1B1 rs11045879 CC genotypes might be a risk factor for the susceptibility to MTX-induced toxicity in children with ALL.
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OBJECTIVE: To investigate the regulation effect of isoniazid on the hepatobiliary membrane transporters multidrug resistance protein 2 (Mrp2), bile salt export pump (Bsep), P-glycoproteins (P-gp), sodium taurocholate cotransporting plypeptide (Ntcp), and which would lay the foundation for the studies of the mechanism on isoniazid-induced liver injury from the level of transporters. METHODS: Following an oral dose of 30, 60, 120 mg · kg-1 · d-1 for 1, 2 and 3 months in mouse respectively, the biochemical indicator of serum were determined; the liver were removed for hepatic pathology; the protein mass of Bsep, Mrp2, Ntcp and P-gp were analyzed by Western Blotting. RESULTS: After high/middle/low dose isoniazid administration, the expression of Mrp2, Bsep, P-gp and Ntcp were all changed, especially the high/middle dose group. In addition, the biochemical and pathological were significantly lagged behind the expression change of the transporters. CONCLUSION: The hepatotoxicity of isoniazid may be associated with excessive hepatic accumulation of the related exogenous substances that medicated by Mrp2, Bsep, P-gp and Ntcp.
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Objective: To investigate the regulatory effect of C-Jun N-terminal kinase (JNK) signal transduction pathway on multi-resistance in the human hepatic cancer Bel-7402/5-fluorouracil (FU) cells, and provide a possible novel target for study on the mechanism of multidrug-resistance in human hepatic cancer cells. Methods: The protein expression levels of JNK and phospho-JNK (p-JNK) in parental human hepatic cancer Bel-7402 cells and the drug-resistant Bel-7402/FU cells were detected by Western blotting. After the inhibition of JNK pathway induced by specific inhibitior SP600125, the expressions of multi-drug resistance 1 (MDR1) mRNA and P-glycoprotein (P-gp) in Bel-7402/FU cells were detected by RT-PCR and immunocytochemistry, respectively. The accumulation and efflux of rhodanmine 123 (Rh123) in the cells were examined by flow cytometry, and the sensitivity to 5-FU of Bel-7402/FU cells was detected by MTT method. Results: The expression of JNK protein was not significantly different between the Bel-7402/FU cells and the parental Bel-7402 cells, but the expression of p-JNK protein in the Bel-7402/FU cells was significantly increased. After inhibition of JNK pathway, the expressions of MDR1 mRNA and P-gp protein were obviously decreased, with a markedly increased accumulation and decreased efflux of Rh123, leading to enhhanced sensitivity to 5-FU of Bel-7402/FU cells. Conclusion: JNK signal transduction pathway is involved in the expressions of MDR1 gene and P-gp in drug-resistant human hepatic cancer Bel-7402/FU cells, and it can regulate the sensitivity to 5-FU of Bel-7402/FU cells.
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Objective: To investigate the effect of Kiwi essence on sensitivity of lung adenocarcinoma xenografts in mice to gemcitabine in combination with cisplatin (DDP) (GP regimen) in mice, and to explore the possible mechanism. Methods: Forty C57BL/6J mice bearing tumor xenografts of Lewis cells were randomized into 5 groups: control group (not tearted with Kiwi essence), high-dose (180 mg/kg) Kiwi essence group, GP group [DDP (3 mg/kg) + gemcitabine (50 mg/kg)], low-dose (60 mg/kg) Kiwi essence combined with GP group, and high-dose (180 mg/kg) Kiwi essence combined with GP group. The growth of tumor xenografts was observed. The mice were sacrificed 20 d after transplantation. The protein and mRNA expression levels of P-glycoprotein (P-gp) and glucose-regulated protein 78 (GRP78) in tumor xenografts were detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Results: The tumor growth was inhibited in various degrees in each drug intervention group as compared with that of the control group, and this inhibition effect was most significant in highdose (180mg/kg) Kiwi essence combined with GP group. The mRNA and protein expression levels of P-gp and GRP78 were significantly decreased in low-dose Kiwi essence combined with GP group, high-dose Kiwi essence group, and high-dose Kiwi essence combined with GP group, as compared with those of the control group and GP group (P < 0.01). The expression levels of P-gp and GRP78 proteins and mRNAs were significantly decreased in high-dose Kiwi essence group and high-dose Kiwi essence combined with GP group as compared with that of the low-dose Kiwi essence combined with GP group. Conclusion: Kiwi essence can obviously reverse the multidrug resistance of lung adenocarcinoma to GP chemotherapy in mice. This mechanism may be associated to the down-regulation of P-gp and GRP78.