Kenley Richard A, Denissenko Mikhail F, Mullin Robert J, Story Jennifer, Ekblom Jonas
Anaborex, Inc., La Jolla, CA 92037, USA.
Oncol Rep. 2008 May;19(5):1113-21.
Our study probed the effects of the beta-2 adrenergic agonist, formoterol and the macrolide antibiotic, roxithromycin, on muscle wasting in a well-characterized animal model of cancer cachexia. Female Wistar rats were inoculated with Yoshida AH130 ascites hepatoma (AH) cells to induce rapid and severe cachexia as demonstrated by wet weight determinations of the hearts, gastrocnemius muscles and carcasses. The control animals received saline (vehicle) inoculations. The AH-inoculated rats were treated once daily for four days by i.p. injection with a vehicle control, 1 mg/kg formoterol, 5 and 50 mg/kg roxithromycin or 1 mg/kg formoterol plus 5, 25, 40 and 50 mg/kg roxithromycin. The saline-inoculated animals were treated by i.p. injection with vehicle control, 1 mg/kg formoterol, 5 and 40 mg/kg roxithromycin. As a result, formoterol alone reduced the loss of muscle mass in the AH-inoculated rats by approximately one-half, consistent with literature reports. Roxithromycin alone at 5 mg/kg did not affect muscle mass in the AH-inoculated rats. Roxithromycin given alone at 50 mg/kg reduced the loss of muscle mass in AH-inoculated animals by approximately one-half. With respect to the antagonizing muscle loss, formoterol combined with either 5 or 25 mg/kg roxithromycin did not reach statistical significance versus formoterol alone, while formoterol plus either 40 or 50 mg/kg roxithromycin enhanced protection against muscle loss versus formoterol alone. The gastrocnemius weights in the AH-inoculated rats treated with formoterol combined with 40 mg/kg roxithromycin were not significantly different from the muscle weights in the saline-inoculated controls. To sum up, formoterol and roxithromycin apparently exert anti-cachectic effects in an additive fashion and may offer the potential for combination therapy in cachexia.
我们的研究探讨了β-2肾上腺素能激动剂福莫特罗和大环内酯类抗生素罗红霉素，对特征明确的癌症恶病质动物模型中肌肉消耗的影响。给雌性Wistar大鼠接种吉田AH130腹水肝癌（AH）细胞，以诱导快速且严重的恶病质，通过对心脏、腓肠肌和尸体的湿重测定来证明。对照动物接受生理盐水（载体）接种。接种AH的大鼠通过腹腔注射载体对照、1mg/kg福莫特罗、5和50mg/kg罗红霉素或1mg/kg福莫特罗加5、25、40和50mg/kg罗红霉素，每天治疗一次，持续四天。接种生理盐水的动物通过腹腔注射载体对照、1mg/kg福莫特罗、5和40mg/kg罗红霉素进行治疗。结果，单独使用福莫特罗使接种AH的大鼠肌肉质量损失减少了约一半，这与文献报道一致。单独使用5mg/kg罗红霉素对接种AH的大鼠肌肉质量没有影响。单独给予50mg/kg罗红霉素可使接种AH的动物肌肉质量损失减少约一半。关于拮抗肌肉损失，福莫特罗与5或25mg/kg罗红霉素联合使用与单独使用福莫特罗相比，未达到统计学显著性，而福莫特罗加40或50mg/kg罗红霉素与单独使用福莫特罗相比，增强了对肌肉损失的保护作用。用福莫特罗联合40mg/kg罗红霉素治疗的接种AH的大鼠的腓肠肌重量与接种生理盐水的对照组的肌肉重量没有显著差异。综上所述，福莫特罗和罗红霉素显然以相加的方式发挥抗恶病质作用，并且可能为恶病质的联合治疗提供潜力。
