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http://dx.doi.org/10.3904/kjim.2016.334

Combination of carboplatin and intermittent normobaric hyperoxia synergistically suppresses benzo[a]pyrene-induced lung cancer  

Lee, Hea Yon (Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Cancer Research Institute, College of Medicine, The Catholic University of Korea)
Kim, In Kyoung (Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Cancer Research Institute, College of Medicine, The Catholic University of Korea)
Lee, Hye In (Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Cancer Research Institute, College of Medicine, The Catholic University of Korea)
Lee, Hwa Young (Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Cancer Research Institute, College of Medicine, The Catholic University of Korea)
Kang, Hye Seon (Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Cancer Research Institute, College of Medicine, The Catholic University of Korea)
Yeo, Chang Dong (Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Cancer Research Institute, College of Medicine, The Catholic University of Korea)
Kang, Hyun Hui (Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Cancer Research Institute, College of Medicine, The Catholic University of Korea)
Moon, Hwa Sik (Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Cancer Research Institute, College of Medicine, The Catholic University of Korea)
Lee, Sang Haak (Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Cancer Research Institute, College of Medicine, The Catholic University of Korea)
Publication Information
The Korean journal of internal medicine / v.33, no.3, 2018 , pp. 541-551 More about this Journal
Abstract
Background/Aims: We explored the effects of intermittent normobaric hyperoxia alone or combined with chemotherapy on the growth, general morphology, oxidative stress, and apoptosis of benzo[a]pyrene (B[a]P)-induced lung tumors in mice. Methods: Female A/J mice were given a single dose of B[a]P and randomized into four groups: control, carboplatin (50 mg/kg intraperitoneally), hyperoxia (95% fraction of inspired oxygen), and carboplatin and hyperoxia. Normobaric hyperoxia (95%) was applied for 3 hours each day from weeks 21 to 28. Tumor load was determined as the average total tumor numbers and volumes. Several markers of oxidative stress and apoptosis were evaluated. Results: Intermittent normobaric hyperoxia combined with chemotherapy reduced the tumor number by 59% and the load by 72% compared with the control B[a]P group. Intermittent normobaric hyperoxia, either alone or combined with chemotherapy, decreased the levels of superoxide dismutase and glutathione and increased the levels of catalase and 8-hydroxydeoxyguanosine. The Bax/Bcl-2 mRNA ratio, caspase 3 level, and number of transferase-mediated dUTP nick end-labeling positive cells increased following treatment with hyperoxia with or without chemotherapy. Conclusions: Intermittent normobaric hyperoxia was found to be tumoricidal and thus may serve as an adjuvant therapy for lung cancer. Oxidative stress and its effects on DNA are increased following exposure to hyperoxia and even more with chemotherapy, and this may lead to apoptosis of lung tumors.
Keywords
Apoptosis; Carboplatin; Hyperoxia; Lung neoplasms; Oxidative stress;
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