Diaporine Potentiates the Anticancer Effects of Oxaliplatin and Doxorubicin on Liver Cancer Cells.
Diaporine Potentiates the Anticancer Effects of Oxaliplatin and Doxorubicin on Liver Cancer Cells.
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DOI：
10.3390/jpm12081318
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发表时间：
2022-08-16
影响因子：
--
通讯作者：
Wu Y
中科院分区：
文献类型：
--
作者：
Tian S;Su R;Wu K;Zhou X;Vadgama JV;Wu Y
近年来的研究表明，地波碱作为一种新型真菌代谢产物，对人非小细胞肺癌和乳腺癌具有较强的体内外抗癌作用。本研究采用3种人肝癌细胞系HepG2、Hep3B和Huh7，评价地阿波碱单用及联合标准细胞毒药物奥沙利铂和阿霉素治疗肝癌的疗效。我们证明地帕泊碱、奥沙利铂和阿霉素触发HepG2细胞数量的浓度和时间依赖性减少。浓度为2.5 μM的地aporine在72 h时几乎100%抑制细胞计数。只有更高浓度（100 μM）的奥沙利铂或阿霉素才能观察到类似的效果。在另外两种肝癌细胞系Hep3B和Huh7中，地帕泊碱、奥沙利铂和阿霉素治疗48小时后，细胞数量也有所减少。这些药物在体外低浓度联用48 h，明显表明地阿波碱提高了对奥沙利铂或阿霉素诱导的癌细胞数量的抑制作用。此外，该组合有效地抑制了菌落的体外生长。我们发现，当地啡与其他药物联合使用时，ERK1/2磷酸化的抑制作用显著增强。此外，我们还发现地帕泊碱与阿霉素或奥沙利铂合用时，其促凋亡作用大大增强。我们进一步发现，治疗后肝癌细胞凋亡的诱导至少部分是由于AKT磷酸化的抑制，导致caspase-3的激活，聚（adp -核糖）聚合酶（PARP）的失活，随后导致DNA损伤，如H2AX水平升高所示。基于这些发现，我们建议地波碱联合标准细胞毒药物奥沙利铂和阿霉素可能在肝癌的治疗中发挥作用。
Recent studies have shown that diaporine, a novel fungal metabolic product, has a strong in vitro and in vivo anticancer effect on human non-small-cell lung and breast cancers. In this study, three human hepatocarcinoma cell lines (HepG2, Hep3B, and Huh7) were used to evaluate the efficacy of diaporine alone and in combination with the standard cytotoxic drugs oxaliplatin and doxorubicin for the treatment of liver cancer. We demonstrated that diaporine, oxaliplatin, and doxorubicin triggered a concentration- and time-dependent decrease in the number of HepG2 cells. Diaporine at a concentration of 2.5 μM showed almost 100% inhibition of cell counts at 72 h. Similar effects were observed only with much higher concentrations (100 μM) of oxaliplatin or doxorubicin. Decreases in cell numbers after 48 h treatment with diaporine, oxaliplatin, and doxorubicin were also demonstrated in two additional hepatoma cell lines, Hep3B and Huh7. The combination of these drugs at low concentration for 48 h in vitro noticeably showed that diaporine improved the inhibitory effect on the number of cancer cells induced by oxaliplatin or doxorubicin. Additionally, this combination effectively inhibited colony growth in vitro. We found that inhibition of phosphorylation of ERK1/2 significantly increased when diaporine was used in combination with other agents. In addition, we also found that when diaporine was used in combination with doxorubicin or oxaliplatin, their proapoptotic effect greatly increased. We further revealed that the induction of apoptosis in hepatoma cells after treatment is due, at least in part, to the inhibition of phosphorylation of AKT, leading to the activation of caspase-3, inactivation of poly (ADP-ribose) polymerase (PARP), and subsequently to DNA damage, as indicated by the increased level of H2AX. Based on these findings, we suggest that diaporine in combination with the standard cytotoxic drugs oxaliplatin and doxorubicin may play a role in the treatment of liver cancer.
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作者：
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作者：
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DOI：
10.2147/dddt.s77341
发表时间：
2015
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Lin X;Farooqi AA;Ismail M
通讯作者：
Ismail M