The multidrug resistance can be reversed for the decrease of P-gp and LRP by inhibiting PI3K/Akt/NF-κB signal pathway in nasopharynx carcinoma

Abstract Aim: To investigate the relationship between PI3K/Akt/NF-κB cellular signal pathway and the expression of P-gp and LRP in multidrug resistance (MDR) cell of nasopharyngeal carcinoma. Method: The PI3K, p-Akt and NF-κB/p65 as the activity of PI3K/Akt/NF-κB were detected by Western blot. The expressions of LRP and P-gp were detected by Western blot and real-time PCR. Result: The RIs of CNE/DDP group to DDP, 5-Fu, VCR, ADR and PTX were 35.04, 18.14, 24.13, 12.00 and 10.18, respectively. The RIs of LY-294002 group were 11.77, 5.83, 3.07, 3.86 and 3.34, and PDTC group were 11.08, 6.55, 7.66, 2.18 and 4.05. The expressions of PI3K, p-Akt and NF-κBp65, LRP and P-gp were increased and mRNA of LRP and P-gp were up-regulated in CNE/DDP. The expression of p-Akt in LY-294002 group was down-regulated. The expression of NF-κB p65 in PDTC group was decreased. The mRNA of LRP and P-gp in LY-294002 group and PDTC group were decreased. Conclusion: MDR of nasopharyngeal carcinoma cell can be regulated by activating PI3K/Akt/NF-κB signal pathway and then increase the expression of P-gp and LRP. The MDR of nasopharyngeal carcinoma cell can be reversed by inhibiting PI3K/Akt/NF-κB signal pathway.

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Effect of fractionated irradiation on the expression of multidrug resistance genes in the CNE1 human nasopharyngeal carcinoma cell line

Molecular Medicine Reports ◽

10.3892/mmr.2012.1148 ◽

2012 ◽

Vol 7 (1) ◽

pp. 187-194 ◽

Cited By ~ 3

Author(s):

XUE-NING JI ◽

FANG YANG ◽

XIAO-MEI SUI ◽

FU-GUANG WANG ◽

RI-GUANG GE ◽

...

Keyword(s):

Multidrug Resistance ◽

Nasopharyngeal Carcinoma ◽

Cell Line ◽

Resistance Genes ◽

Carcinoma Cell ◽

Carcinoma Cell Line ◽

Fractionated Irradiation ◽

Nasopharyngeal Carcinoma Cell ◽

Human Nasopharyngeal Carcinoma ◽

Multidrug Resistance Genes

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Multidrug resistance in chronic lymphocytic leukemia

Orvosi Hetilap ◽

10.1556/oh.2008.28203 ◽

2008 ◽

Vol 149 (4) ◽

pp. 161-167 ◽

Cited By ~ 1

Author(s):

Tamás Szendrei ◽

Tamás Magyarlaki ◽

Gábor Kovács ◽

Ágnes Nagy ◽

Árpád Szomor ◽

...

Keyword(s):

Multidrug Resistance ◽

Chronic Lymphocytic Leukemia ◽

Real Time ◽

Real Time Pcr ◽

Lymphocytic Leukemia ◽

Light Cycler ◽

Mdr 1

Az utóbbi években krónikus lymphoid leukaemiában új prognosztikai faktorok vizsgálata került a figyelem középpontjába. A citogenetikai eltérések, az immunglobulin-nehézlánc génmutációs státusza, a CD38- és ZAP70-expresszió mind a közelmúltban megismert prognosztikus faktorok, de kevés az adat a multidrog-rezisztencia jelentőségéről. Célok: A tanulmány célja genetikai, expressziós és funkcionális szinten jellemezni 82 krónikus lymphoid leukaemiában szenvedő beteg multidrog-rezisztenciájának sajátosságait, és vizsgálni azok összefüggését a betegek túlélésével és a kezelésre adott válasszal. Módszerek: a szerzők 66 betegnél vizsgálták az MDR-1 gén ben – Light Cycler Real Time PCR segítségével meghatározott – „Single Nucleotid Polymorphism” sajátosságot, amely irodalmi adatok szerint a P-glikoprotein expresszióját befolyásolja. Összesen 82 betegnél áramlási citometria során anti-P-glikoprotein monoklonális antitest segítségével a P-glikoprotein- expresszió t, az ún. calcein-verapamil teszttel pedig a multidrog-rezisztencia funkcióját vizsgálták. A kezelésre adott választ 35 betegnél vizsgálták, a statisztikai elemzésnél Fischer-tesztet alkalmazva. A túlélési analízist a teljes beteganyagon elvégezték ( n = 82, Log-rank-teszt). Eredmények: Az irodalmi adatokkal ellentétben a szerzők nem találtak korrelációt a vizsgált három multidrogrezisztencia-teszt között. A kezelésre adott választ vizsgálva 35 kezelt betegből 13 nonrespondernek, 22 pedig respondernek bizonyult. A P-glikoprotein-pozitív fenotípusú esetek ( n = 9) 89%-ban klinikailag nonrespondernek bizonyultak (9 P-glikoprotein-pozitív krónikus lymphoid leukaemiás beteg közül 8 nonresponder volt), a P-glikoprotein-negatív esetek ( n = 26) pedig 80%-ban jó terápiás választ mutattak (26 P-glikoprotein-negatív beteg közül 21 responder) ( p < 0,001). Az átlagos várható túlélésben is jelentős, bár nem szignifikáns ( p = 0,106) különbséget észleltek (84 vs 203 hónap). Következtetések: A vizsgált három laboratóriumi paraméter közül a P-glikoprotein sejtfelszíni jelenléte a leginkább releváns adat krónikus lymphoid leukaemiában a kemorezisztencia előjelzésére és a túléléssel kapcsolatban is prognosztikai faktorként értékelhető.

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DNA Methylation Inhibites ANXA1 Gene Expression in Nasopharyngeal Carcinoma Cell Lines*

PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS ◽

10.3724/sp.j.1206.2009.00170 ◽

2009 ◽

Vol 36 (10) ◽

pp. 1319-1326 ◽

Cited By ~ 3

Author(s):

Shuang-Xiang TAN ◽

Rui-Cheng HU ◽

Ai-Guo DAI ◽

Cen-E TANG ◽

Hong YI ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Nasopharyngeal Carcinoma ◽

Cell Lines ◽

Carcinoma Cell ◽

Nasopharyngeal Carcinoma Cell ◽

Carcinoma Cell Lines

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KLK11 promotes the activation of mTOR and protein synthesis to facilitate cardiac hypertrophy

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-02053-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yi Wang ◽

Hongjuan Liao ◽

Yueheng Wang ◽

Jinlin Zhou ◽

Feng Wang ◽

...

Keyword(s):

Protein Synthesis ◽

Angiotensin Ii ◽

Cardiac Hypertrophy ◽

Western Blot ◽

Real Time ◽

Real Time Pcr ◽

Mtor Signaling ◽

Heart Weight ◽

Cardiomyocyte Hypertrophy ◽

Quantitative Real Time Pcr

Abstract Background Cardiovascular diseases have become the leading cause of death worldwide, and cardiac hypertrophy is the core mechanism underlying cardiac defect and heart failure. However, the underlying mechanisms of cardiac hypertrophy are not fully understood. Here we investigated the roles of Kallikrein 11 (KLK11) in cardiac hypertrophy. Methods Human and mouse hypertrophic heart tissues were used to determine the expression of KLK11 with quantitative real-time PCR and western blot. Mouse cardiac hypertrophy was induced by transverse aortic constriction (TAC), and cardiomyocyte hypertrophy was induced by angiotensin II. Cardiac function was analyzed by echocardiography. The signaling pathway was analyzed by western blot. Protein synthesis was monitored by the incorporation of [3H]-leucine. Gene expression was analyzed by quantitative real-time PCR. Results The mRNA and protein levels of KLK11 were upregulated in human hypertrophic hearts. We also induced cardiac hypertrophy in mice and observed the upregulation of KLK11 in hypertrophic hearts. Our in vitro experiments demonstrated that KLK11 overexpression promoted whereas KLK11 knockdown repressed cardiomyocytes hypertrophy induced by angiotensin II, as evidenced by cardiomyocyte size and the expression of hypertrophy-related fetal genes. Besides, we knocked down KLK11 expression in mouse hearts with adeno-associated virus 9. Knockdown of KLK11 in mouse hearts inhibited TAC-induced decline in fraction shortening and ejection fraction, reduced the increase in heart weight, cardiomyocyte size, and expression of hypertrophic fetal genes. We also observed that KLK11 promoted protein synthesis, the key feature of cardiomyocyte hypertrophy, by regulating the pivotal machines S6K1 and 4EBP1. Mechanism study demonstrated that KLK11 promoted the activation of AKT-mTOR signaling to promote S6K1 and 4EBP1 pathway and protein synthesis. Repression of mTOR with rapamycin blocked the effects of KLK11 on S6K1 and 4EBP1 as well as protein synthesis. Besides, rapamycin treatment blocked the roles of KLK11 in the regulation of cardiomyocyte hypertrophy. Conclusions Our findings demonstrated that KLK11 promoted cardiomyocyte hypertrophy by activating AKT-mTOR signaling to promote protein synthesis.

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