The Effect Of Hyperbaric Oxygen On Prostate Cancer Cell Line And Its Potential Role In Therapy For Prostate Cancer

BACKGROUNDWith the development of China and diet changed,the overall incidence of prostate cancer in men increased annually and became a more and more serious healthy problem to the elderly man.Between 1985 and 2005,the incidence of prostate cancer in men increased from 2.6 per 100,000 to 10 per 100,000 in ShangHai territory,an increase of approximately 300%.Hyperbaric oxygen(HBO)—100 percent oxygen at two to three times the atmospheric pressure at sea level—can result in arterial oxygen tension in excess of 2000 mmHg and oxygen tension in tissue of almost 400 mmHg.HBO increases oxygen tensions and oxygen delivery to tissues independent of hemoglobin.Such doses of oxygen have a number of beneficial biochemical,cellular,and physiologic effects. Over the past 50 years,HBO therapy has been recommended and used in a wide variety of medical conditions.In theory,HBO may remove the hypoxic stimulus;that drives tumour angiogenesis and other adaptations that facilitate tumour growth in a hypoxic environment,thus sensitizing them to radiotherapy,chemotherapy and other therapeutic treatment modalities.Although serious adverse events are rare,HBO cannot be regarded as an entirely benign intervention.In 1966 Johnson and Lauchlan first reported a tumor-stimulatory effect with HBO,demonstrating increased metastases in patients with cervical cancer.The effect of HBO administration on tumour growth has been inconclusive.HBO has been previously contraindicated in the treatment of malignancy due to concern that an increased oxygen pressure may stimulate tumour growth via re-oxygenation of hypoxic tumour cells and increased neovascularization.It has further been suggested that HBO may increase the incidence and/or rate of growth of local recurrence or remote metastatic disease in patients with a history of malignancy.Although most of the experimental and clinical studies suggest that HBO has no direct effect on tumors,there is a considerable amount of conflicting evidence to support the idea that HBO has an effect.The general consensus is that HBO could not kill tumor cells directly and remains ineffective as a stand-alone therapy.However,HBO may enhance the efficacy of certain therapies that are limited because of the hypoxic tumor microenvironment.But the exact effect of HBO on the natural history of malignancy is uncertain. Minimal evidence exists regarding the direct effect of HBO on prostate cancer cells. And there are no experimental studies showing treatment with HBO during other therapeutic treatment modalities is to improve the response of prostate cancer.The experimental studies could answer the following questions:1.Does HBO accelerate the growth of indolent prostate cancer cells(suggesting HBO administration is safe when it is used to manage patients treated by other therapies for prostate cancer)?2.HBO may improve the ability of other therapies to kill hypoxic prostate cancer cells. As an adjuvant therapy,HBO may result in a reduction in mortality and recurrence?OBJECTIVE1.To detect the effects of HBO on human prostate LNCaP and PC-3 cell lines.2.Assess HBO potential role in therapy for prostate cancer.METHODS1.Human prostate LNCaP and PC-3 cell lines were randomized to undergo 5 sessions of either HBO or normobaric air in standardized conditions.Microscope and transmission electron microscope were used to detect the cell morphosis.2.Detect LNCaP and PC-3 cell lines proliferation in response to HBO by the CCK-8 assay.3.Observe the effection of HBO on LNCaP and PC-3 cell cycle by FCM.4.Transwell system were used to assess HBO effect on LNCaP and PC-3 cell migration.5.Form prostate cancer PC-3 cell xenografts,and analysis of developed tumours' grow up.At the end of the experiment detect xenografts's microvessel density(MVD),apoptosis markers(p53,p27 protein) and proliferative index(Ki-67 protein) by immunohistochemistry.RESULTS1.Exposure to HBO at 2.5 atm for 5 treatment sessions comprised a daily 70-min session had no effect on LNCaP and PC-3 cells' proliferation,ultramicro morphosis and cell migration in vitro.2.HBO induced LNCaP and PC-3 cell lines to enter the cell cycle and accumulated them in G₂/M stage.3.No differences were observed in volume of prostate cancer PC-3 cell xenografts, tumour microvessel density,proliferative index and apoptosis markers compared to the control group(p＞0.05).CONCLUSIONSHBO did not have a tumour stimulatory effect on prostate cancer and may potentially be used safely as an adjuvant therapy.HBO therapy may improve therapeutic efficacy of prostate cancer. Further research may be warranted pending outcomes of the clinical research in evaluating the adjunctive potential of HBO with other therapeutic treatment modalities.