Antitumor effects of two bisdioxopiperazines against two experimental lung cancer models in vivoReportar como inadecuado




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BMC Pharmacology

, 4:32

First Online: 24 December 2004Received: 03 October 2004Accepted: 24 December 2004

Abstract

BackgroundProbimane Pro, an anti-cancer agent originating in China, was derived from razoxane ICRF-159, Raz, a drug created in Britain, specifically targeting at cancer metastasis and as a cardioprotectant of anthrocyclines. Pro and Raz are bisdioxopiperazine compounds. In this work, we evaluated the anti-tumor and anti-metastatic effects of Pro and Raz in vivo against two lung tumor models, one of murine origin Lewis lung carcinoma, LLC and one of human origin LAX-83.

ResultsAfter determining the lethal dosage of Pro and Raz, we assessed and compared the inhibitory effects of Pro and Raz against primary tumor growth and metastatic occurrences of LLC at the dosage of LD5. Pro and Raz were active against primary tumor growth and significantly inhibited pulmonary metastasis of LLC at same dose-ranges inhibitory rates > 90 %. Both Raz and Pro were effective in 1, 5, and 9 day administration schedules. Three different schedules of Raz and Pro were effective against the primary tumor growth of LLC 35–50 %. The synergistic anticancer effect of Raz with bleomycin Ble from 41.3 % to 73.3 % was more obvious than those with daunorubicin Dau from 33.1 % to 56.3 % in the LLC tumor model. Pro was also seen to have synergistic anti-cancer effects with Ble in the LLC model. Both Raz and Pro inhibited the growth of LAX 83 in a statistically significant manner.

ConclusionsThese data suggest that both Raz and Pro may have anti-tumor potentiality and Raz and Pro have combinative effects with Ble or Dau. The potential targets of bisdioxopiperazines may include lung cancers, especially on tumor metastasis. The anti-cancer effects of Raz and Pro can be increased with the help of other anticancer drugs.

List of abbreviation used areProprobimane

Razrazoxane

CaMcalmodulin

LPOlipoperoxidation

Daudaunorubicin

Blebleomycin

LLCLewis lung carcinoma

LAX-83a lung adenocarcinoma xenograft

ADRadriamycin

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2210-4-32 contains supplementary material, which is available to authorized users.

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Autor: Da-Yong Lu - Bin Xu - Jian Ding

Fuente: https://link.springer.com/







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