Figure 8.

Schematic diagram of the intracellular signaling pathway following sequential treatment with celecoxib and bortezomib in human colorectal cancer cells. The expression of p53 is required for ER stress-mediated Ca²⁺ translocation to promote autophagy-associated cell death following the sequential treatment with celecoxib and bortezomib. The consecutive treatment of colon cancer cells with celecoxib and bortezomib also enhances autophagy-associated cell death in p53^−/− colon cancer cells. ER, endoplasmic reticulum; JNK, c-Jun N-terminal kinase; p38 MAPK, p38 mitogen-activated protein kinase; LAMP1, lysosomal-associated membrane protein 1; LC3-I/II, microtubule-associated protein 1A/1B-light chain 3.