Cisplatin (CDDP)-based chemotherapy resistance is a major challenge for lung cancer treatment. PKM2 is the rate-limiting enzyme of glycolysis, which is associated with CDDP resistance. KAT8 is an acetyltransferase that regulates lung cancer progression. Thus, we aimed to explore whether KAT8 regulates PKM2 acetylation to participate in CDDP resistance. CDDP resistance was analyzed by CCK-8, flow cytometry and western blotting. To explore the regulation of KAT8 on PKM2, coimmunoprecipitation (Co-IP), immunofluorescence and immunoprecipitation followed by western blotting were performed. Glycolysis was determined using glucose consumption, lactate production, ATP level detection kits and extracellular acidification rate assay. We observed that KAT8 levels were downregulated in CDDP-treated A549 and PC9 cells. Interference with KAT8 inhibited cell viability, promoted apoptosis and upregulated PARP1 and cleaved-PARP1 levels of A549 cells treated with CDDP, suggesting the sensitivity to CDDP was enhanced, while KAT8 overexpression attenuated the CDDP sensitivity. Moreover, KAT8 interacted with PKM2 to promote the PKM2 K433 acetylation. PKM2 K433 mutated plasmids inhibited the si-KAT8-regulated cell viability, apoptosis and glycolysis compared with PKM2-WT. Besides, KAT8 reversed the inhibition of tumor growth caused by CDDP. In conclusion, KAT8-mediated PKM2 K433 acetylation was associated with the resistance of lung cancer cells to CDDP. The findings may provide a new idea for the treatment of CDDP-resistant lung cancer.
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http://dx.doi.org/10.1097/CAD.0000000000001622 | DOI Listing |
Lung Cancer
December 2024
State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address:
Background: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare subtype of non-small-cell lung cancer. This study aims to compare the efficacy and safety of perioperative PD-1/PD-L1 inhibitor plus chemotherapy versus chemotherapy alone in stage II-IIIB PLELC patients.
Patients And Methods: This retrospective study included stage II-IIIB PLELC patients.
Lung Cancer
December 2024
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
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Background: Previous observational studies examining the relationship between cadmium exposure and various cancers have yielded conflicting results. This study aims to comprehensively clarify the relationship between blood cadmium concentration (BCC) and nine specific cancers.
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World J Surg Oncol
December 2024
Department of Radiation Oncology, Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou, Guangdong, 510095, People's Republic of China.
Background: The combination of immunotherapy and chemotherapy has demonstrated an enhancement in progression-free survival (PFS) for individuals with advanced and metastatic triple-negative breast cancer (TNBC) when compared to the use of chemotherapy alone. Nevertheless, the extent to which different subgroups of metastatic TNBC patients experience this benefit remains uncertain.
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Cancer Imaging
December 2024
Department of Translational Imaging in Oncology, National Center for Tumor Diseases (NCT/UCC) Dresden, Medical Faculty and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Fetscherstraße 74, Dresden, 01307, Germany.
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