Pancreatic cancer, whilst not one of the most common cancers, is associated with high mortality rates – with only 5-10% of those patients surviving 5 years after diagnosis. Pancreatic cancer is often not responsive to chemotherapy or immunotherapy. Surgery is extensive and, depending on the severity of the disease, is not possible for a significant proportion of patients.
For patients with non-resectable stages of pancreatic cancer or distant metastasis, systemic chemotherapy is used as a first-line treatment, employing various drugs such as gemcitabine (GEM), capecitabine, and 5-florouracil, either alone or in combination with radiotherapy.
The difficulties in treating pancreatic cancer are likely because of the tumour-associated microenvironment. The pancreatic cancer microenvironment consists of stromal cells, lacks vascularisation, and cancer cells are adapted to survive in long-term hypoxic conditions.
Hypoxic conditions, or hypoxia, can induce aggressive characteristics of various forms of cancer. Under hypoxia, tumour cells can develop several mechanisms for evading apoptosis (cell death).
What is Oxygen-Ozone Therapy?
Oxygen-Ozone (O2/O3) therapy is an alternative treatment option that has been used in several clinical disorders including HIV, SARS, circulatory disorders, and cancer. O2/O3 therapy has been seen to increase tissue oxygenation, and ozone therapy has been seen to improve chronic pain and inflammation, including that induced by hypoxia.
In addition, O2/O3 therapy has also been found to inhibit the growth of various human tumour cells, including breast, colon, and ovarian. Significantly, the therapy does not affect non-tumour cell lines and enhances the effect of chemotherapeutic drugs.
Cannabinoids and Cancer Treatment
A growing number of studies have aimed to understand the potential benefits of cannabinoids in cancer treatment. Cannabinoids have been found to reduce cancer cell viability, proliferation, metastasis, and induce cancer cell death in human forms of cancer including glioblastoma multiforme, multiple myeloma, colorectal cancer, endometrial cancer, prostate carcinoma, and melanoma. However, some studies have also demonstrated conflicting responses.
Cannabidiol (CBD) is the most common non-psychotropic compound of the cannabinoids produced by Cannabis Sativa L.. CBD interacts with various receptors, including the CB1 and CB2 receptors of the endocannabinoid system. Activation of cannabinoid receptors – particularly CB2 – has been seen to encourage pancreatic cell apoptosis (death), without affecting normal cells.
In addition, an in vivo murine study found that a combination of CBD and GEM increased survival length by almost three times when compared with vehicle or with GEM alone. Another study revealed that a combination of GEM and CB1 ligand SR141716 reduced tumour growth in mice in comparison to control and mice treated with a single agent.
CBD in Combination with Chemotherapy Drugs
One study has aimed to understand the potential anticancer effects of CBD and O2/O3, separately, and in combination. Researchers assessed the effects on two human pancreatic cancer cell lines – PANC-1 and MiaPaCa-2. For comparison, a combination of GEM and Paclitaxel (PTX) – the main chemotherapeutical drugs used for the treatment of pancreatic cancer – were also assessed.
It was found that both CB1 and CB2 receptors are expressed in both cancer cell lines while CB2 protein levels are higher in the PANC-1 cell line. The researchers summarised that PDAC cells express significant levels of most of CBD’s target receptors. It was also found that CBD is more effective in reducing cell viability in pancreatic cancer cell lines than in normal cells.
Possibly one of the most interesting findings of the study was that CBD can induce apoptotic cell death and reduces cell migration of PDAC cell lines. Some doses of CBD may also have the potential to increase the cytotoxicity of chemotherapy drugs GEM and PTX.
CBD in Combination with O2/O3 Therapy
The researchers assessed the effects of O2/O3 therapy on pancreatic cancer cell lines. As well as the addition of CBD administration in O2/O3-treated cell lines was evaluated. They find that the addition of O2/O3 strongly reduces cell viability. This effect was also enhanced by CBD in a dose and time-dependent manner.
Cell death was examined 24 hours after treatment with CBD and O2/O3. It was found that O2/O3 is able to induce cell death in both cell lines and CBD-O2/O3 increased the percentage of cells that underwent apoptosis.
Both cell lines were also treated with chemotherapy drugs following treatment with both CBD and O2/O3. The results showed that CBD-O2/O3 treatment plus chemotherapeutic drugs increased the cytotoxic activity shown by O2/O3 alone, as well as by chemotherapeutic drugs in combination with CBD, without O2/O3.
The researchers concluded that both alone and in combination, CBD and O2/O3 were able to induce significant changes in the expression profile of genes strongly involved in pancreatic cancer. This suggests that further study on this combination should be carried out to better understand the potential of combined CBD and O2/O3 in the progression of pancreatic cancer.