Chemotherapy remains one of our best treatments against cancer but, frustratingly, cancer cells can develop resistance to these drugs. Now, researchers at Zhengzhou University have found that bursts of calcium can weaken their defense mechanism from the inside, making drugs effective once more.
Cancer cells can defend themselves against drugs that would be toxic to them in a pretty clever way. They produce a pump protein called P-glycoprotein (P-gp), which resides in the cell membrane and if drugs get inside the tumor cell the P-gp uses a molecule called adenosine triphosphate (ATP) to pump them back out.
This process can have the unfortunate effect of giving cancer multidrug resistance (MDR), rendering chemotherapy ineffective and reducing survival rates for particular cancers. In past studies, scientists have tried to counter this resistance by targeting either P-gp or ATP, but so far haven’t been able to do so effectively or safely enough.
Previous studies have revealed calcium ions to be one promising weapon in the fight to reverse resistance, showing promise in decreasing the levels of both P-gp and ATP. So for the new study, the researchers investigated how to get calcium inside the cancer cells to work its magic.
The team developed what they call calcium ion nanogenerators (TCaNG). These nanoparticles are made of calcium phosphate and contain a chemotherapy drug called doxorubicin, and finally are coated with molecules that guide them to cancer cells. Once the nanogenerators make their way inside the tumors, the acidic environment there disintegrates them, releasing calcium ions and the drug.
The concoction seemed to work well in lab experiments. When tested on cancer cells in a dish, the team observed that the levels of both ATP and P-gp went down, and the doxorubicin was able to kill the tumors – even though they’d previously shown resistance to drugs. Follow-up tests in mice with cancer showed that the tumors shrank after 21 days, and the treatment didn’t appear to cause any side effects.
Of course, at this early stage it has yet to be tested in humans, so there’s no guarantee that the results would carry across. But the early results are nevertheless promising.
The research was published in the journal Nano Letters.
Source: American Chemical Society