Reversal of multidrug resistance by icaritin in doxorubicin-resistant human osteosarcoma cells / 中国天然药物

Multidrug resistance (MDR) is one of the major obstacles in cancer chemotherapy. Our previous study has shown that icariin could reverse MDR in MG-63 doxorubicin-resistant (MG-63/DOX) cells. It is reported that icariin is usually metabolized to icariside II and icaritin. Herein, we investigated the effects of icariin, icariside II, and icaritin (ICT) on reversing MDR in MG-63/DOX cells. Among these compounds, ICT exhibited strongest effect and showed no obvious cytotoxicity effect on both MG-63 and MG-63/DOX cells ranging from 1 to 10 μmol·L. Furthermore, ICT increased accumulation of rhodamine 123 and 6-carboxyfluorescein diacetate and enhanced DOX-induced apoptosis in MG-63/DOX cells in a dose-dependent manner. Further studies demonstrated that ICT decreased the mRNA and protein levels of multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 1 (MRP1). We also verified that blockade of STAT3 phosphorylation was involved in the reversal effect of multidrug resistance in MG-63/DOX cells. Taken together, these results indicated that ICT may be a potential candidate in chemotherapy for osteosarcoma.

Reversal of multidrug resistance by icaritin in doxorubicin-resistant human osteosarcoma cells / 中国天然药物

Multidrug resistance (MDR) is one of the major obstacles in cancer chemotherapy. Our previous study has shown that icariin could reverse MDR in MG-63 doxorubicin-resistant (MG-63/DOX) cells. It is reported that icariin is usually metabolized to icariside II and icaritin. Herein, we investigated the effects of icariin, icariside II, and icaritin (ICT) on reversing MDR in MG-63/DOX cells. Among these compounds, ICT exhibited strongest effect and showed no obvious cytotoxicity effect on both MG-63 and MG-63/DOX cells ranging from 1 to 10 μmol·L. Furthermore, ICT increased accumulation of rhodamine 123 and 6-carboxyfluorescein diacetate and enhanced DOX-induced apoptosis in MG-63/DOX cells in a dose-dependent manner. Further studies demonstrated that ICT decreased the mRNA and protein levels of multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 1 (MRP1). We also verified that blockade of STAT3 phosphorylation was involved in the reversal effect of multidrug resistance in MG-63/DOX cells. Taken together, these results indicated that ICT may be a potential candidate in chemotherapy for osteosarcoma.

Research of Xiaoyan Decoction on multidrug resistance of lung adenocarcinoma A549/DDP cell with cisplatin resistance in human gene / 中草药

Objective: To study the Xiaoyan Decoction serum influence the expression level of lung adenocarcinoma that cisplatin-resistent of A549/DDP cell multidrug resistance-associated protein 1 (MRP1), lung resistance-related protein (LRP), MRP mRNA, and LRP mRNA, to find out Xiaoyan Decoction's target to the chemotherapy resistance, and to lay foundation for the clinical of reversing lung cancer chemotherapy resistance. Methods: The A549 nude mice hypodermic tumor model was given an equal amount of saline, 2 mg/kg of cisplatin, low and high doses of Xiaoyan Decoction (20, 40 g/kg), and then the serum was gain. The cisplatin resistance of human lung adenocarcinoma A549/DDP cell line was chosen as acquired drug-resistance model, Xiaoyan Decoction on MDR of A549/DDP cell gene expression product of multidrug resistance-associated protein 1, lung resistance-related protein and its effect on mRNA expression level was detected by Western blotting and RT-PCR technique. Results: Compared with the control group, the expression of MRP1 and LRP protein decreased gradually (P<0.05) as the serum drug concentration of Xiaoyan Decoction increased. The level of LRP mRNA and MRP1 mRNA in low and high doses of Xiaoyan Decoction group also decreased, and much more obvious inhibition of gene expression was observed as the increasing of drug concentration. Conclusion: Different serum drug concentration of Xiaoyan Decoction can differently control the expression of MRP1, LRP protein, MRP1 mRNA, and LRP mRNA, with the increasing of serum drug concentration, the decreasing of expression level, namely positive-correlated to the dose, which indicates that Xiaoyan Decoction Reversal of the lung cancer drug resistance the might related to the MRP1 and LRP.

Studies on effects and mechanisms of P-gp and MRP1 inhibitor on transportation of gastrodin / 中草药

Objective: To study the effects and mechanisms of p-glycoprotein (P-gp) inhibitor and MRP1 inhibitor on the transportation of gastrodin (GAS). Methods: Cell toxicity of GAS was detected by MTT assay, molecular Docking was employed to predicted binding mode and effect ability of GAS with P-gp and MRP1. MDCK-MDR1 cell model was employed to study the influences of Ver, a P-gp inhibitor, and Probenecid, a MRP1 inhibitor, on the transportation of GAS. Results: There was no cell cytotoxicity of GAS between the concentration of 100 to 1000 μg/mL. There was hydrogen-bond and hydrophobic interaction between P-gp and GAS, and hydrogen-bond, hydrophobic interaction and electrostatic-interaction between MRP1 and GAS. LibDock Score indicated that both P-gp-verapamil (Ver) and MRP1-Probenecid were more stable than P-gp-GAS and MRP1-GAS. The Papp of GAS BL→AP was greater than that of AP→BL, Efflux ratio (ER) of GAS was about 1.5, which indicated the efflux pump protein might involve the transportation of GAS. The Papp of GAS was significant increased but the ER of GAS was significant decreased when co-administrated with Ver (P<0.05). The Papp of GAS was slightly increased and the ER of GAS was slightly decreased when co-administrated with Probenecid, while there was no significance. Conclusion: The results indicate that GAS is the substrate of P-gp. However, whether GAS is the substrate of MRP1 needs further research. Both Ver and Probenecid could enhance the transportation of GAS by competitive binding with P-gp and MRP1.

Expression of MRP1 and CD34 in colorectal carcinoma tissue and its clinical significance / 中国基层医药

ObjectiveTo explore the expression of MRP1 and CD34 in colorectal carcinoma tissue and the relationship with clinicopathological factors.MethodsImmunohistochemical streptavidin-perosidase method was used to examine the expression of MRP1 and CD34 in 53 cases with colorectal carcinoma and normal colorectal tissue.The correlation between the levels of MRP1and CD34 expression and clinicopathological factors were analyzed.ResultsThe positive expression rates of MRP1 in the carcinoma group and normal colorectal tissue group were 49.1％ and 15.1％ respectively,and there was a significant difference of the positive expression between the two groups( x2 =14.029,P ＜ 0.01 ).The expression of MRP1 had no correlation with the degree of differentiation,the depth of invasion,the metastasis of lymph node and all the other clinicopathological factors ( P ＞ 0.05 ).CD34 value in the carcinoma group and normal colorectal tissue group were ( 35.63 ± 12.23 ) MVD/HP and ( 6.12 ± 0.97) MVD/HP,respectively,and there was a significant difference between the two groups (t =17.565,P ＜ 0.01 ).CD34 was not correlated with age,sex,tumor size,localization of the primary tumor ( P ＞ 0.05 ),but correlated with Dukes staging,lymph node metastasis,differentiation of the tumor,depth of invasion( all P ＜ 0.05).ConclusionThe overexpression of MRP1 and CD34 protein may involve in colorectal carcinogenesis;MRP1 may involve in the primary multidrug resistance in colorectal carcinoma.; CD34 may involve in the colorectal carcinoma invasion and metastasis.Investigating the expression of MRP1 and CD34 in colorectal carcinoma simultaneously can provide new referential indexes for the treatment and prognosis of colorectal carcinoma.

Análise da expressão e atividade das moléculas de influxo e de efluxo de drogas em células da leucemia mielóide crônica / Analysis of the expression and activity of drug influx and efflux molecules in chronic myeloid leukemia cells

"A leucemia mielóide crônica (LMC) é caracterizada pela presença da translocação t(9:22) que codifica a proteína quimérica oncogênica BCR-ABL. Imatinibe é uma droga alvo-específica que inibe a atividade tirosina quinase (TK) da proteína BCR-ABL. Entretanto, os níveis intracelulares do imatinibe podem ser alterados pelas proteínas transportadoras de efluxo de drogas: glicoproteína P (Pgp), proteína da resistência em câncer de mama (BCRP) e proteína relacionada à resistência à múltiplas drogas (MRP1), assim como a proteína transportadora de influxo de drogas (OCT1). O objetivo do presente estudo foi analisar a participação dessas proteínas, isoladamente ou em associação, na resistência ao imatinibe em linhagens celulares e células de pacientes com LMC. Para análise da atividade das proteínas transportadoras de efluxo, foi utilizado o fluorocromo rodamina-123 associado ao modulador ciclosporina-A (Rho+CSA) e o pheophorbide A associado ao fumitremorgin C (PhA+FTC), ambos através de citometria de fluxo. A análise dos RNAm dos genes ABCB1, ABCG2 e SLC22A1 que codificam as proteínas Pgp, BCRP e OCT1, respectivamente, foi realizada por PCR em tempo real. A inibição da TK BCR-ABL foi mensurada através dos níveis de fosforilação de CrkL (pCrkL), seu principal alvo de ativação. Observamos uma maior positividade para o ensaio Rho+CSA nas amostras que expressavam Pgp comparada com as que expressavam MRP1, sugerindo menor atividade dessa proteína em pacientes com LMC, ou ainda que tal ensaio possa ser menos específico para a atividade da MRP1. O ensaio PhA+FTC foi capaz de identificar a atividade da proteína BCRP em linhagens celulares e células de pacientes. Níveis reduzidos dos RNAm ABCB1 e SLC22A1, mas não do RNAm ABCG2, foram observados quando comparados com as amostras de indivíduos saudáveis. Não houve correlação entre os níveis da proteína Pgp e do RNAm ABCB1. A expressão de Pgp foi detectada na maioria das amostras de LMC, independente da fase da doença, e não foi associada com o prognóstico desfavorável. Variações nos níveis de expressão da Pgp foram observadas durante a evolução da LMC e relacionadas com o tratamento prévio. O imatinibe foi capaz de aumentar a expressão da Pgp, assim como os níveis do RNAm ABCB1 na linhagem K562-Lucena 1, Pgp+. Além disso, observamos uma maior redução de pCrkL e um maior percentual de morte celular nas células K562, Pgp-, quando comparadas à K562-Lucena 1, evidenciando um possível papel do imatinibe como substrato para a Pgp. Este fármaco também demonstrou ter potencial para funcionar como agente modulador da bomba de efluxo, uma vez que impediu o exporte de Rho das células K562-Lucena 1. Amostras de pacientes resistentes ao imatinibe exibiram altos níveis de atividade das proteínas transportadoras de efluxo de drogas (ensaio Rho+CSA). Nossos dados mostram que a atividade e/ou expressão dos transportadores de efluxo e influxo de drogas encontram-se alterados na maioria dos pacientes com LMC, porém não há correlação com a resposta ao imatinibe e o prognóstico na LMC. Entretanto, o conjunto dos resultados sugere um papel para a Pgp na resistência in vitro ao imatinibe"(AU)

"Chronic myeloid leukemia (CML) is characterized by the presence of the t(9:22) encoding the BCR-ABL chimeric oncogenic protein. Imatinib is a target specific drug that inhibits the activity of the tyrosine kinase (TK) protein BCR-ABL. However, imatinib intracellular concentration may be altered by transporter proteins. It was described that efflux proteins, P-glycoprotein (Pgp), breast cancer resistance protein (BCRP) and multidrug resistance related protein (MRP1), and the influx protein, the organic cation transporter protein (OCT1) may contribute for imatinib clinical resistance. The aim of this study was to evaluate the role of these proteins in imatinib resistance in cell lines and leukemic cells from CML patients. To analyze the activity of the efflux transporter proteins, fluorochrome rhodamine-123 associated with the modulator cyclosporin A (Rho+CSA) and pheophorbide A associated with fumitremorgin C (PhA+FTC) were used by flow cytometry. Analysis of ABCG1, ABCG2 and SLC22A1 genes, that encode the Pgp, BCRP and OCT1 proteins, respectively, was performed by real time PCR. The inhibition of BCR-ABL TK was measured by the levels of CrkL phosphorylation (pCrkL), its main target of activation. We observed a higher positivity for Rho+CSA assay in samples expressing Pgp, when compared with the ones expressing MRP1. These results suggest that patients with CML have lower activity of this protein, or this assay might be less specific to indicate the activity of MRP1. The PhA+FTC assay was able to identify BCRP activity in cell lines and cells from patients. Reduced levels of ABCB1 and SLC22A1, but not ABCG2 mRNA were observed when compared with samples from healthy individuals. There was no correlation between the levels of Pgp protein and ABCB1 mRNA. Pgp expression was detected in most samples of CML, regardless of disease stage and was not associated with poor prognosis. Changes in Pgp expression levels have been observed during the development of CML and were related to pretreatment. Imatinib was able to increase Pgp expression as well as ABCB1 mRNA levels in Pgp+ K562Lucena 1 cells. Moreover, we observed a greater pCrkL reduction and a higher percentage of cell death in Pgp- K562 cells compared to K562-Lucena 1, indicating a possible role of imatinib as a Pgp substrate. This drug has also been shown to have potential as an efflux pump modulating agent, once efflux of Rho was prevented in K562-Lucena 1. Imatinib resistant patient samples exhibited high levels of efflux transporter proteins activity (Rho+CSA assay). Our data show that the activity and / or expression of influx and efflux transporters of drugs are altered in most patients with CML, but no correlation with prognosis and response to imatinib in CML was observed. However, our results suggest a role for Pgp in imatinib resistance"(AU)

Experimental study of MRP1 gene expression of adenovirus-mediated hairpin RNA inhibition of arsenic trioxide resistant K562/AS2 cell line / 白血病·淋巴瘤

Objective To construct a recombinant adenovirus vector of Hairpin RNA specific for MRP1 gene and study its inhibition of MRP1 gene expression in K562/AS2 cell line resistant to AS_2O_3 (ATO). Methods A MRP1-specific hairpin RNA recombinant adenovirus vector was constructed and used to infected K562/AS2 cells. Expression level of MRP1 mRNA detected by real-time fluorescent quantitative PCR. MRP1 protein detected by flow cytometry. MTT method was used to detected the cytotoxicity of ATO and etoposide. Results MRP1 mRNA and protein expression level in K562/AS2 cells before and after the pAd-MRPl-shRNA adenovirus infection was (34.70±0.28 vs 4.19±0.03, P <0.05) and (26.40±0.16 vs 10.85±0.37, P<0.05), respectively. RR of K562/AS2 to arsenic trioxide and etoposide was (11.4078±0.3183 fold vs 1.6126±0.3015 fold, P<0.05) and (5.9141 ±0.0149 fold vs 1.7664±0.1038 fold, P <0.05), respectively. The reversal fold of ATO and etoposide was (7.2409±1.3668) and (3.3555±0.1886), respectively. Conclusion Successfully constructed pAd-EGFP-U6-shRNA-MRPl adenovirus vector, the vector of infection K562/SA2 cells can inhibit MRP1 gene expression and reverse the resistance of the ATO and etoposide.

Clinical significance of SKP2 and MRP-1/CD9 expression in glottic carcinoma and adjacent tissues / 临床耳鼻咽喉头颈外科杂志

Objective:To study the expression of SKP2 and MRP-1/CD9 protein in glottic cancer and adjacent tissues,and to analyze its significance for a safe surgical margin.Method:Thirty-eight cases of glottic squamous cell carcinoma were studied for its cancer tissue, tissue 2 mm, 5 mm , and 10 mm away from cancer ,and 10 cases of vocal cord polyp were served as control. SKP2 and MRP-1/CD9 protein were examined by immunoh istochemical method.Result:The positive expression of SKP2 proteins decreased in sequence of polyp mucosa, those adjacent to carcinoma (10 mm, 5 mm, 2 mm ) and cancer tissue, and there was significant difference between them(P<0.05);On the contrary, the positive expression of the MRP-1/CD9 proteins increased in sequence of polypusmucosa, those adjacent to carcinoma (10 mm,5 mm, 2 mm) and cancer tissue,and there was significant difference between them (P<0.05).Conclusion:SKP2 and MRP-1/CD may act as the reference index for judging the biological speciality of LSCC. It is appropriate to regard 5 mm or above 5 mm away from tumors as a safe margin for surgical treatment of glottic carcinoma.

Inhibitional effect of small hairpin RNA on expression of MRPI gene in K562/AS2 cell line resistant to As2O3 / 白血病·淋巴瘤

Objective To investigate the inhibitional effect of MRPI-shRNA on expression of MRP1gene in K56.2/AS2 cells resistant to arsenic trioxide. Methods Three pieces of MRPI-shRNA were designed,synthesized and transfected into K562/AS2 cells with lipesome. Expression level of MRPI mRNA were determined by real time fluorescent quantitative PCR. MRPI protein expression and intracellular accumulation of DNR were assayed with flow cytometry. Results After treated with MRPI-shRNA, the expression level of MRPI mRNA and MRPI protein in K562/AS2 cells decreased significantly(79.1±0.07) % and (62.48±0.86) %,respectively (P <0.05). The intracellular accumulation of DNR increased significantly(P < 0.05). Conclusion MRPI-shRNA can down-regulate the expression of MRPI gene in K562/AS2 cell line.

Silencing of Multidrug Resistance-Associated Protein(MRP1) Expression by siRNAs / 中国生物化学与分子生物学报

Three pSIREN-siRNA plasmids were constructed using a pSIREN-RetroQ vector to silence the expression of muhidrug resistance-associated protein (MRP1) gene, and subsequently characterized by restriction endonuclease digestion and DNA sequencing. A truncated MRP1 and a full-length MRP1 were cloned into pEGFP-N2 and PeDNA3.1 respectively as pEGFP-MRP1T and pcDNA-MRP1. The plasmid pEGFP-MRP1T was co-transferred with each of the three pSIREN-siRNAs into HEK293 cells for MRP1T-GFP targeted silencing, and pSIREN-siRNA1 was used as the negative control, pSIREN-siRNA2 and pSIREN-siRNA3 appeared to be more effective to silence MRP1T-GFP compared to pSIREN-siRNA1 as shown by fluorescence microscopy. For the silencing of full-length MRP1 expression, HEK293 ceils were co-transferred with pcDNA-MRP1 and either of the three pSIREN-siRNAs, then subjected for Western blot analysis and MTT assays, pSIREN-siRNA2 and pSIREN-siRNA3 were able to inhibit the expression of 190 kD MRP1, but not pSIREN-siRNA1. The MDR of MRP1-transfected HEK293 ceils was abolished with pSIREN-siRNA2 or pSIREN-siRNA3 transfections. RNA secondary structure predictions demonstrated that the mRNA local free energy (△G) of the siRNA1 targeted sequence was lower, as the GC content and Tm value of siRNA1 were higher than those of siRNA2 and siRNA3. These data suggest that the local structure siRNAs and target mRNA may influence the silencing efficiency of MRP1 expression.

Expression of KAI1/CD82 and MRP-1/CD9 in Transitional Cell Carcinoma of Bladder / 华中科技大学学报（医学）（英德文版）

The expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder (TCCB) and its clinical significance were investigated. Immunohistochemistry was used to detect KAI1/CD82 and MRP-1/CD9 protein expression in 52 TCCB specimens. Correlation between the expression of KAI1/CD82 and MRP-1/CD9 to clinicopathologic factors was statistically analyzed. The results showed that the positive rate of KAI1/CD82 and MRP-1/CD9 in TCCB was 50% and 61.5%, respectively. The MRP-1/CD9 and KAI1/CD82 expression was significantly associated with grade of TCCB (P＜0.05), but no correlation was found between MRP-1/CD9 or KAI1/CD82 expression and clinical stage of TCCB (P＞0.05). The expression level of MRP-1/CD9 and KAI1/CD82 in recurrent TCCB samples was lower than that in non-recurrent samples (P＜0.05). Meanwhile, the correlation between the KAI1/CD82 expression and MRP-1/CD9 expression was statistically significant (r=0.316, P＜0.05). It was concluded that KAI1/CD82 and MRP-1/CD9 expression may be important prognostic indicators and potentially useful for assessing the biological behavior of TCCB.

The Roles of Four Multi-drug Resistance Proteins in Hepatocellular Carcinoma Multidrug Resistance / 华中科技大学学报（医学）（英德文版）

The roles of multi-drug resistance protein 1 (MDR1), multi-drug resistance related protein 1 (MRP1), lung resistance protein (LRP) and breast cancer resistance protein (BCRP) in the multi-drug resistance (MDR) of hepatocellular carcinoma (HCC) were studied. By exposing HepG2 cell line to progressively increased concentrations of adriamycin (ADM), HepG2 multi-drug resistant subline (HepG2/ADM) was induced. The MDR index of HepG2/ADM was detected by using MTT.The expressions of the four MDR proteins in the three cell lines (L02, HepG2, HepG2/ADM) were investigated at mRNA and protein levels by real-time RT-PCR and Western blot respectively. Our results showed that when the ADM concentration was under 100 μg/L, HepG2 could easily be induced to be drug-resistant. The IC50 of the HepG2/ADM to ADM was 282 times that of HepG2. The expression of MDR1 and BCRP mRNA in HepG2/ADM cells were 400 and 9 times that of HepG2 cells respectively while there was no difference in the mRNA expressions of MRP1 and LRP. There was no difference between HepG2 and L02 cells in the mRNA expressions of the four genes. At the protein level, the expressions of MDR1, BCRP and LRP but MRP1 in HepG2/ADM were significantly higher than those of HepG2 and L02. Between HepG2 and L02,there was no difference in the expressions of four genes at the protein level. HepG2/ADM is a good model for the study of MDR. The four genes are probably the normally expressed gene in liven The expressions of MDR1 and BCRP could be up-regulated by anti-cancer agents in vitro. The MDR of HCC was mainly due to the up-regulation of MDR1 and BCRP but MRP1 and LRP. These findings suggest they may serve as targets for the reversal of MDR of HCC.

Expression of MRP1/CD_9 in cervical squamous cell carcinoma tissue and its clinical significance / 肿瘤研究与临床

Objective To investigate the clinical significance in MRP1/CD_9 expression in cervical squamous cancer tissues and normal cervical tissues.Methods The expression of MRP1/CD_9 were assayed by SABC immunohistochemical methods in 53 cases of cervical cancer tissues and 13 cases of normal cervical tissues.Results Positive expression of MRP1/CD_9 was detected in 13 normal cervical tissue.MRP1/D_9 ex- pression is down-regulated in cervical carcinoma(P

Refractory Factors in Head and Neck Cancer: ATP Binding Cassette Transporters Expressed in Head and Neck Cancer Cell Lines / Oral Science International

The aim of the present study was to clarify whether ATP binding cassette transporters are refractory factors in head and neck cancer chemotherapy. For <i>in vitro</i> and <i>in vivo</i> chemotherapeutic studies, we employed a human salivary gland adenocarcinoma cell line (HSY) and a human oral squamous cell carcinoma cell line (SCCSK) with vincristine (VCR) at clinically equivalent doses. Western blot analysis, reverse transcription-polymerase chain reaction, <i>in vivo</i> evaluation in xenograft models inoculated with cultured carcinoma cell line and drug efflux analysis were performed. VCR-treated SCCSK and HSY cells, as well as xenografted SCCSK and HSY cells in tumor-bearing nude mice, were found to express MDR1/ABCB1 and MRP1/ ABCC1. In addition to MDR1 and MRP1 mRNA, HSY/VCR and its cloned cells expressed MRP7/ABCC10 mRNA, but SCCSK/VCR did not express MRP7. Furthermore, drug resistance to VCR and docetaxel decreased in HSY/VCR in the presence of a competitive MRP7 inhibitor, 17-beta-estradiol-(17-beta-D-glucuronide). These results indicate that MDR1 and MRP1 expression are refractory factors in head and neck cancer chemotherapy and suggest that induction of MRP7 expression is involved in drug resistance in salivary gland adenocarcinomas.

Effect of Trastuzumab in Combination with IFN α-2b on HER2 and MRP1 of ACHN / 华中科技大学学报（医学）（英德文版）

Summary: To study the effect of Trastuzumab in combination with IFN α-2b on HER2 and MRP1 of ACHN in vitro, ACHN cell line of RCC was cultured by employing cell culture. The tetrazolium-based colorimetric assay was used to evaluate the growth-inhibiting effect of Trastuzumab with IFN α-2b. SP method was utilized to determine the expression of HER2 and MRP1 of the cells. Our results showed that Trastuzumab had inhibitory effect on the growth of renal tumor cells and reversing effect on the multi-drug-resistance (MDR) in RCC in a time- and dose-dependent manner. Treated with Trastuzumab with or without IFN α-2b, the expression of HER2 and MRP1 genes of RCC was decreased significantly (P<0.05). It was concluded that Trastuzumab with IFN α-2b could inhibit the proliferation of RCC and the expression of HER2 and MRP1 of ACHN and to some extent, reverse the MDR of the tumor cells.

Correlation of Immunohistochemical Expression of MDR1, MRP1, Topoisomerase IIalpha with Prognostic Factors and Histoculture Drug Response Assay (HDRA) Result in Breast Carcinoma / 한국유방암학회지

PURPOSE: Drug resistance plays an important role in the failure of chemotherapy in breast cancer. The purpose of the study was to investigate the chemosensitive and chemoresistance indices of breast carcinomas and see if the in vitro chemosensitivity test correlated with the prognostic indices. METHODS: The immunohistochemical expressions of MDR1, MRP1 and topoisomerase IIalpha(topo IIalpha) were studied and then correlated these with the in vitro chemosensitivities using the histoculture drug response assay (HDRA) and clinicopathological factors in 51 breast carcinomas. RESULTS: In the breast carcinomas examined, the immunohistochemical expressions of MDR1, MRP1 and topo II alpha were strongly observed in 26 (51.0%), 16 (32.0%), 15 (31.3%) carcinomas, respectively. The MRP1 was more frequently expressed in poorly differentiated carcinomas (P= 0.006), and those of MDR1 and topo II alpha were more frequently observed in tumor overexpressing cerbB2 (P=0.038, P=0.036). The expression of MDR1 was related to that of topo II alpha (P=0.015). Comparing these markers with the in vitro chemosensitivities to cyclophosphamide, 5-FU, adriamycin, taxol and taxotere, no correlations were found between the expression of MDR1, MRP1, and topo II alpha but from the chemosensitivity using the HDRA, the growth inhibition rate for cyclophosphamide was higher in MRP1 expressing carcinomas (P=0.009). CONCLUSION: MDR1, MRP1 and topo II alpha were all found to be associated with the poor prognostic indices, but assessment of their immunohistochemical expressions did not allow for prediction of the response to chemotherapy by the in vitro chemosensitivity test in breast carcinomas.