Blocking an enzyme that produces the sugar molecule sialic acid increased the sensitivity of cervical cancer cells to chemotherapy. This suggests that developing drugs against the factor might be a way to improve treatment response in patients with cervical cancer.
The study, “Knockdown of ST6Gal-I increases cisplatin sensitivity in cervical cancer cells,” was published in the journal BMC Cancer.
Resistance to chemotherapy is a major problem when treating cervical cancer. Researchers from China’s Bengbu Medical College and Anhui Medical University noted that earlier studies showed that the enzyme sialyltransferase I, as well as its product, sialic acid, were increased in other types of cancers.
But investigators had not explored whether the enzyme is also involved in cervical cancer and if it might influence a tumor’s capacity to spread or become resistant to treatment.
The research team first examined lab-grown cervical cancer cells in which they silenced the gene coding for sialyltransferase I. This decreased the amount of the enzyme in the cells to 13.2 percent of natural levels.
When cells lacking the enzyme were treated with the chemotherapy drug Platinol-AQ (cisplatin), they died to a much larger extent than cells with the enzyme intact; 28.8 percent compared to only 7.9 percent in cells retaining the enzyme. Without the enzyme, the cells also largely lost their invasive ability.
The results in lab-grown cells prompted the team to test how silencing the enzyme would impact cancer characteristics in mice. Researchers injected mice with human cervical cancer cells. Half the group received cells in which the enzyme had first been silenced. Mice then received either Platinol-AQ treatment or saline as a control condition.
After four weeks, mice with normal tumors which had been treated with chemotherapy showed some signs of improvement compared to untreated mice. But those lacking the enzyme sialyltransferase I had considerably smaller tumors after receiving Platinol-AQ, suggesting that the lack of the enzyme made cancer cells more vulnerable to the effects of chemotherapy.
When examining tumors under the microscope, the team also confirmed that those lacking sialyltransferase I had lower levels of the anti-apoptotic marker BCL-2, confirming that the cancer cells lacking the enzyme had increased cisplatin sensitivity in cervical cancer cells.