Effect of Hypercapnia, an Element of Obstructive Respiratory Disorder, on Pancreatic Cancer Chemoresistance and Progression

Influence of the Hypercapnic Tumor Microenvironment on the Viability of Hela Cells Screened by a CO2-Gradient-Generating Device

“…27 On the contrary, Nevler et al reported an increased colony formation and proliferation rate in both MIA-PaCa-2 and Panc-1 cell lines, which were subjected to a 10% CO 2 environment as compared to the 5% CO 2 controls for up to 5 days. 7 In another study, Hela cells were cultured with 8 and 16 mmHg of 100% CO 2 stimulating the CO 2 pneumoperitoneum environment in vitro for 1, 2, 3, and 4 h. In the 100% CO 2 setting, the cells increased the ability of proliferation after a short time of inhibition and reduced the ability of invasion, migration, and adhesion accordingly. 28 In our present study, thanks to the wide-ranged CO 2 levels offered by our platform for observing the chronic response of cells in time course, to our interest, we have found that the hypercapnic microenvironment influenced cell proliferation in a time-dependent manner and also depended on CO 2 concentrations.…”

“…Zhu et al have investigated the effects of elevated pCO 2 levels on the growth of the Chinese hamster ovary (CHO) cells, and they found that an increase in the pCO 2 level from 60 to 100 mmHg did not affect cell growth significantly, while the highest pCO 2 level (150 mmHg) could suppress cell growth by about 9% . On the contrary, Nevler et al reported an increased colony formation and proliferation rate in both MIA-PaCa-2 and Panc-1 cell lines, which were subjected to a 10% CO 2 environment as compared to the 5% CO 2 controls for up to 5 days . In another study, Hela cells were cultured with 8 and 16 mmHg of 100% CO 2 stimulating the CO 2 pneumoperitoneum environment in vitro for 1, 2, 3, and 4 h. In the 100% CO 2 setting, the cells increased the ability of proliferation after a short time of inhibition and reduced the ability of invasion, migration, and adhesion accordingly .…”

“…For example, an earlier in vitro study demonstrated that when CO 2 concentration changes from 5 to 20%, it could enhance the invasive capacity of colon cancer cells, 4 and a 10% CO 2 environment would lead to an increasing colony formation and proliferation rate in both MIA-PaCa-2 and Panc-1 cell lines than the 5% CO 2 culture condition. 7 On the contrary, other studies have mentioned that chronic hypercarbia would lead to decreased cell growth, 8 or incubation with high CO 2 concentration alone has no effect on cancer cells. 4 Studies have also suggested that the hypercapnic tumor microenvironment may confer chemoresistance to lung cancer cells by reprogramming mitochondrial metabolism in vitro.…”

“…Earlier research had shown that excess CO 2 production is responsible for the acidification of tumor tissues and increased pCO 2 values (59–84 mmHg) have been found in solid tumors. , However, the biological effects of elevated CO 2 levels on cancer cells remained controversial. For example, an earlier in vitro study demonstrated that when CO 2 concentration changes from 5 to 20%, it could enhance the invasive capacity of colon cancer cells, and a 10% CO 2 environment would lead to an increasing colony formation and proliferation rate in both MIA-PaCa-2 and Panc-1 cell lines than the 5% CO 2 culture condition . On the contrary, other studies have mentioned that chronic hypercarbia would lead to decreased cell growth, or incubation with high CO 2 concentration alone has no effect on cancer cells .…”

“…On the contrary, other studies have mentioned that chronic hypercarbia would lead to decreased cell growth, or incubation with high CO 2 concentration alone has no effect on cancer cells . Studies have also suggested that the hypercapnic tumor microenvironment may confer chemoresistance to lung cancer cells by reprogramming mitochondrial metabolism in vitro . , Concerns also exist that pneumoperitoneum with the introduction of 100% CO 2 in abdominal insufflation may be associated with tumor cell migration and invasion . It is worth mentioning that CO 2 concentration and exposure time duration varied in these available reports, leading to controversial findings regarding the effects of hypercapnia on cells.…”