Improved radiosensitizing effect of the combination of etanidazole and paclitaxel for hepatocellular carcinoma in vivo

Yang,Yanling; Jin,Cheng; Li,Haimin; He,Yong; Liu,Zhaohui; Bai,Ling; Dou,Kefeng

doi:10.3892/etm.2011.389

February 2012 Volume 3 Issue 2

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February 2012 Volume 3 Issue 2

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Article

Improved radiosensitizing effect of the combination of etanidazole and paclitaxel for hepatocellular carcinoma in vivo

Authors:
- Yanling Yang
- Cheng Jin
- Haimin Li
- Yong He
- Zhaohui Liu
- Ling Bai
- Kefeng Dou
View Affiliations / Copyright

Affiliations: Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, P.R. China, Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, P.R. China, Department of Rehabilitation Medicine, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, P.R. China, Department of Clinical Laboratories, Xi'an Gaoxin Hospital, Xi'an 710075, P.R. China
Pages: 299-303
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Published online on: November 24, 2011

https://doi.org/10.3892/etm.2011.389
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Abstract

Hepatocellular carcinoma (HCC) is one of the most critical global health issues. Potential curative therapies, including surgical resection, are offered to only a limited number of patients. Therefore, new and effective treatment strategies are required. Recently, radiotherapy with hypoxic radiosensitizers has shown promise in cancer therapy. Our previous study demonstrated that radiosensitization produced by etanidazole and paclitaxel was additive in vitro. This study was carried out to determine the synergistic effect of the two drugs in murine HCC H22 cell xenograft-bearing BALB/c mice in vivo. The morphology of the transplanted tumors was observed. The drug content in the blood and tumors of mice was measured by high-performance liquid chromatography. The radiosensitizing effect on H22 cell xenograft‑bearing mice was evaluated in terms of tumor growth inhibition and survival. Expression of hypoxia inducible factor-1α (HIF-1α) was studied using immunohistochemistry. The morphological consequences on the H22 xenografts were consistent with the pathological characteristics of HCC. There was no significant difference in drug content in the blood and tumors between single drug and combination administration. The combination of the two drugs improved the radiosensitizing effect in vivo compared to single drug administration in an animal model. The changes in HIF-1α expression indirectly verified the above-mentioned results. This study may provide a new combination of radiosensitizers for HCC radiotherapy.

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1.	World Health OrganizationMortality databaseWHO statistical information system. http://www.who.int/whosis/. Accessed July 2008.
2.	DM ParkinF BrayJ FerlayP PisaniGlobal cancer statistics, 2002CA Cancer J Clin5574108200510.3322/canjclin.55.2.74
3.	S PadmaJB MartinieDA IannittiLiver tumor ablation: percutaneous and open approachesJ Surg Oncol100619634200910.1002/jso.2136420017157
4.	T IchidaDH van ThielT HassaneinThe medical management of hepatocellular carcinoma (HCC) in Japan: a review with implications for HCC seen in the westHepatogastroenterology431575158319968975968
5.	J BruixM ShermanPractice Guidelines Committee, American Association for the Study of Liver DiseasesManagement of hepatocellular carcinomaHepatology4212081236200510.1002/hep.20933
6.	JM LlovetMI RealX MontanaR PlanasS CollJ AponteArterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trialLancet35917341739200210.1016/S0140-6736(02)08649-X
7.	BA TeicherHypoxia and drug resistanceCancer Metast Rev1339681994
8.	DM BrizelGS SibleyLR ProsnitzRL ScherMW DewhirstTumor hypoxia adversely affects the prognosis of carcinoma of the head and neckInt J Radiat Oncol Biol Phys38285289199710.1016/S0360-3016(97)00101-69226314
9.	J OvergaardHypoxic radiosensitization: adored and ignoredJ Clin Oncol2540664074200710.1200/JCO.2007.12.787817827455
10.	P WardmanChemical radiosensitizers for use in radiotherapyClin Oncol (R Coll Radiol)19397417200710.1016/j.clon.2007.03.01017478086
11.	CN ColemanTH WassermanRC UrtasunJ HalseyVK HirstS HancockPhase I trial of the hypoxic cell radiosensitizer SR-2508: the results of the five to six week drug scheduleInt J Radiat Oncol Biol Phys1211051108198610.1016/0360-3016(86)90236-13017904
12.	RB TishlerPB SchiffCR GeardEJ HallTaxol: a novel radiation sensitizerInt J Radiat Oncol Biol Phys22613617199210.1016/0360-3016(92)90888-O1346533
13.	ME WattsMF DennisM WoodcockUptake and additivity of the radiosensitizing effects of Ro 03-8799 and SR-2508 in mammalian cells in vitroBr J Radiol6012331235198710.1259/0007-1285-60-720-12332961396
14.	C JinL BaiG GuoRadiosensitization by the combination of SR-2508 and paclitaxel in hypoxic human tumor cells in vitroJ Radiat Res48179185200710.1269/jrr.0610517420623
15.	C JinL BaiH WuF TianG GuoRadiosensitization of paclitaxel, etanidazole and paclitaxel+etanidazole nanoparticles on hypoxic human tumor cells in vitroBiomaterials28372437302007
16.	J SeongChallenge and hope in radiotherapy of hepatocellular carcinomaYonsei Med J50601612200910.3349/ymj.2009.50.5.60119881961
17.	S MaB JiaoX LiuH YiD KongL GaoApproach to radiation therapy in hepatocellular carcinomaCancer Treat Rev36157163201010.1016/j.ctrv.2009.11.00820031332
18.	SH KerrDJ KerrNovel treatments for hepatocellular cancerCancer Lett286114120200910.1016/j.canlet.2009.07.00119664880
19.	CC HudsonM LiuGG ChiangDM OtternessDC LoomisF KaperRegulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycinMol Cell Biol2270047014200210.1128/MCB.22.20.7004-7014.200212242281
20.	JI BárdosM AshcroftNegative and positive regulation of HIF-1: a complex networkBiochim Biophys Acta1755107120200515994012

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Improved radiosensitizing effect of the combination of etanidazole and paclitaxel for hepatocellular carcinoma in vivo

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Abstract

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