Korean J Intern Med.  2018 May;33(3):541-551. 10.3904/kjim.2016.334.

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

• Lee HY
• Kim IK
• Lee HI
• Lee HY
• Kang HS
• Yeo CD
• Kang HH
• Moon HS
• Lee SH

• KMID: 2411582
• DOI: http://doi.org/10.3904/kjim.2016.334

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.

Keyword

Apoptosis; Carboplatin; Hyperoxia; Lung neoplasms; Oxidative stress

MeSH Terms

Animals
Apoptosis
Carboplatin*
Caspase 3
Catalase
DNA
Drug Therapy
Female
Glutathione
Humans
Hyperoxia*
Lung Neoplasms*
Lung*
Mice
Oxidative Stress
RNA, Messenger
Superoxide Dismutase
Tumor Burden
Carboplatin
Caspase 3
Catalase
DNA
Glutathione
RNA, Messenger
Superoxide Dismutase