The invention belongs to the technical field of medicines, and discloses a method for promoting
drug resistance of
triple negative breast cancer bevacizumab by driving IGF2BP3
lactic acid modification through PARK7, and milk
acylation modification (IGF2BP3-K76lac) of
lysine at the 76th site of IGF2BP3
protein is a key driving factor of
drug resistance of
bevacizumab. The overexpression of the IGF2BP3-K76lac can obviously enhance the
drug resistance of the
bevacizumab, and the overexpression of the IGF2BP3-K76lac is verified in both in-vitro experiments and in-vivo models. From the perspective of a
molecular mechanism, the milk
acylation modification at the IGF2BP3K76 site can enhance the binding capacity of the IGF2BP3K76 site and m6A modified FSP1 mRNA, so that the expression level of FSP1 is up-regulated, and finally the cells are endowed with
ferroptosis resistance. By blocking the IGF2BP3-K76lac,
ferroptosis induced by bevacizumab can be remarkably enhanced, the
antioxidant defense mechanism of an
organism is destroyed, and
tumor growth is inhibited. In addition, PARK7 functions as a milk
acyltransferase, and enhances the
binding ability of IGF2BP3-K76lac to promote the function thereof. And finally, the
blocking antibody targeting IGF2BP3-K76lac is proved to have a synergistic effect with the bevacizumab, so that the sensitivity of the bevacizumab is effectively recovered.