Combination of carboplatin and intermittent normobaric hyperoxia synergistically suppresses benzo[a]pyrene-induced lung cancer
Open accessAbstract
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.
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Intermittent normobaric hyperoxia (95% O2) can promote the toxic effects of carboplatin on lung tumors.
“Additionally, intermittent normobaric hyperoxia (95% O2) can promote the toxic effects of carboplatin on lung tumors. 383”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [383]
The cytotoxicity of first-line chemotherapeutics, such as cisplatin, carboplatin, DOX, paclitaxel, and 5-fluorouracil, is enhanced in the presence of hyperoxia.
“The cytotoxicity of first‐line chemotherapeutics, such as cisplatin, carboplatin, DOX, paclitaxel, and 5‐fluorouracil, is enhanced in the presence of hyperoxia (Table 2). 383 , 389 , 399 , 400 , 401 , 402”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [383]
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- Authors
- Lee, H. Y., Kim, I. K., Lee, H. I., Lee, H. Y., Kang, H. S., Yeo, C. D., Kang, H. H., Moon, H. S., & Lee, S. H.
- Affiliations
- Catholic University of Korea (KR)
- Corresponding author
- Lee, Sang Haak
- Venue
- The Korean Journal of Internal Medicine
- Published
- 2018-05-01
- Volume
- 33
- Issue
- 3
- Pages
- 541-551
- ISSN
- 1226-3303 (ISSN-L)
- 2005-6648
- PMC
- PMC5943660
- OpenAlex
- W2771583235
- Cited by
- 19
- References
- 32
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 8 · 2021: 1 · 2020: 3
- FWCI
- 0.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- The Korean Journal of Internal Medicine (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Research Foundation of Korea
- Ministry of Education (2014R1A1A2058026)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- normobaric hyperoxia, carboplatin, benzo[a]pyrene, lung cancer, chemoprevention, oxidative stress, apoptosis, DNA damage, 8-hydroxy-2'-deoxyguanosine, Bax/Bcl-2 ratio, caspase-3, adjuvant therapy, tumor growth inhibition
- MeSH terms
- Animals, Antineoplastic Agents, Benzo(a)pyrene, Female, Japan, Lung, Lung Neoplasms, Random Allocation, Carboplatin, Hyperoxia, Mice
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