ABSTRACT

Gemcitabine (GEM) is an anti-cancer drug that has been used in the treatment of a wide range of human cancers. However, cancer cells developing resistance to GEM which may limit its use. So, adjuvant therapies either enhance the effects of GEM or overcome resistance are needed for the treatment of cancer. In this study, we examined the influence of the interaction between γ-radiation (RAD) and GEM against HepG2 cells acquired resistance to GEM. Based on our data, the combination therapy elevates ROS production, induces endoplasmic reticulum (ER)-stress response machinery, up-regulates caspase-3 and p53 as well as boosts PTEN proficiency which blocked PI3K/AKT pathway that inhibits IκB/NF-κB signaling. It could be concluded that therapeutic strategies of gemcitabine in cancer might be potentiated by radiotherapy to reach better therapeutic outcomes.

摘要

吉西他滨（GEM）是一种抗癌药物，已用于治疗多种人类癌症。然而，癌细胞对GEM产生抗性可能限制其使用。因此，需要辅助疗法来增强GEM的作用或克服耐药性以治疗癌症。在这项研究中，我们检查了γ射线（RAD）和GEM之间的相互作用对HepG2细胞获得的对GEM的抗性的影响。根据我们的数据，联合疗法可提高ROS的产生，诱导内质网（ER）应激反应机制，上调caspase-3和p53的表达，并增强PTEN能力，从而阻断PI3K / AKT途径，从而抑制IκB/NF-κB信号。可以得出结论，吉西他滨在癌症中的治疗策略可能通过放疗得到加强，以达到更好的治疗效果。