Hyperbaric Oxygen Potentiates Doxil Antitumor Efficacy by Promoting Tumor Penetration and Sensitizing Cancer Cells

Abstract

Hypoxia is a fundamental hallmark of solid tumors and helps contribute to chemotherapy resistance. Hyperbaric oxygen (HBO) therapy can overcome tumor hypoxia and promote chemotherapy antitumor efficacy; however, the simultaneous administration of some conventional chemotherapies, including doxorubicin (DOX), with HBO is considered an absolute contraindication. Here, DOX‐loaded liposome (Doxil) is coadministered with HBO to assess the safety and efficacy of this combination treatment. By overcoming tumor hypoxia, HBO not only improves Doxil tumor penetration by decreasing the collagen deposition but also sensitizes tumor cells to Doxil. As a result, the combination treatment synergistically inhibits H22 tumor growth, with a tumor inhibition rate of 91.5%. The combination of HBO with Doxil shows neither extra side effects nor promotion of tumor metastasis. These results collectively reveal that the combination of HBO with Doxil is an effective and safe treatment modality. As both HBO and Doxil are routinely used, their combination could quickly translate to clinical trials for patients with hypoxic solid tumors.

Hypoxia Alters the Expression of CC Chemokines and CC Chemokine Receptors in a Tumor–A Literature Review

“…Then not only will HIF transcriptional activity be reduced but also the expression of many genes, including the discussed chemokines. The positive effects of anti-hypoxia treatment have also been shown in hyperbaric oxygen therapy which uses oxygen at a pressure higher than atmospheric pressure at the sea level [280,281]. Hyperbaric oxygen therapy has a strong preventive effect on hypoxia, common in many cancers [282][283][284][285].…”

“…Hyperbaric oxygen therapy has a strong preventive effect on hypoxia, common in many cancers [282][283][284][285]. It will affect all neoplastic mechanisms in the tumor, which in combination with other anti-cancer drugs may be an effective therapeutic approach against one of the most common human diseases [281,286].…”

The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors—A Review of Literature

“…For this reason, research focuses on inhibitors of the transcriptional activities of HIF-1 and HIF-2 [ 297 ]. On the other hand, oxygen concentration may be increased in the tumor and thus hypoxia may be prevented by using hyperbaric oxygen therapy [ 298 , 299 ]. However, as hypoxia is also important in the functioning of hematopoietic stem cells under physiological conditions [ 300 , 301 , 302 ], any therapy against hypoxia may also cause side effects which affect the production of various blood cells.…”

Hyperbaric Oxygen Therapy Represses the Warburg Effect and Epithelial–Mesenchymal Transition in Hypoxic NSCLC Cells via the HIF-1α/PFKP Axis

“…Moreover, HBO therapy can inhibit tumor growth in some cancers (e.g., breast carcinoma), but there is limited evidence of HBO’s efficacy in other cancer types (e.g., cervical and bladder carcinomas) ( 7 ). Currently, HBO is being more rigorously investigated as an adjuvant therapy to enhance the efficacy of conventional radio- and photodynamic therapies against certain solid tumors ( 8 ). Although clinical evidence regarding HBO therapy in NSCLC patients remains limited ( 9 ), HBO has been shown to rescue CoCl 2 -induced hypoxic NSCLC cells from dedifferentiation and apoptosis resistance in vitro ( 10 ).…”