植物多酚和塞来昔布的新方案可提高化疗药物对培养癌细胞的抗癌效果和选择性

IF 3.4 3区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Journal of Dental Sciences Pub Date : 2024-07-01 DOI:10.1016/j.jds.2024.02.013
Ming-Yung Chou , Shoei-Yn Lin-Shiau
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引用次数: 0

摘要

探索提高化疗药物疗效和选择性的新型方案是解决癌症治疗问题的当务之急。本研究旨在探索植物多酚[姜黄素(C)、茶多酚(G)或 GC]与塞来昔布(Cl)和硫酸锌的协同抗癌效果。药物对培养的癌细胞和病原生物膜的抗增殖作用分别通过 MTT 和光密度(OD600)进行检测;对外流泵(Na-K-ATPase)的抑制作用则通过比色法进行检测。协同(CI < 1)抗癌效果通过组合指数(CI)和药效指数(EI)方程进行评估。Cl 和单独的甲氨蝶呤(MTX)不仅对培养癌细胞的增殖和外排泵有抑制作用,而且对致病生物膜的形成也有抑制作用。植物多酚(P)和 MTX 增强了 Cl 的这些抑制作用。此外,含有 Cl、美金刚(Mem)或硫利达嗪(TRZ)的新方案不仅进一步增强了抗癌效果和选择性,还分别增强了对四种化疗药物(MTX、顺铂、5-氟尿嘧啶和多柔比星)的外排泵和致病性生物膜形成的抑制作用。在这项研究中,由植物多酚(P)、靶向药物(T;Cl、Mem 或 TRZ)和金属离子(M;ZnSO)组成的新型方案(即 PTM 方案)不仅本身具有抑制作用,而且还显著增强了四种化疗药物的抗癌功效和选择性。由于这些组合新方案能有效抑制外排泵和病原体生物膜的形成,因此有望克服多药耐药性癌症的问题,值得进一步临床研究。
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Novel regimens of phytopolyphenols and celecoxib enhancing efficacy and selectivity of anticancer effects of chemotherapeutic agents on cultured cancer cells

Background/purpose

Explorations of novel regimens enhancing efficacy and selectivity of chemotherapeutic agents are urgent to solve the problems of cancer therapy. This study aimed to explore synergistic anticancer effects of novel regimens of phytopolyphenols [curcumin (C), tea polyphenols (G) or GC] with celecoxib (Cl) and ZnSO4.

Materials and methods

Antiproliferative effects of drugs on cultured cancer cells and pathogenic biofilms were assayed by MTT and optical density (OD600) respectively; their inhibition on efflux pump (Na+-K+-ATPase) was measured by colorimetric methods. Synergistic (CI < 1) anticancer effects were evaluated by the equations of combination index (CI) and efficacy index (EI).

Results

Both Cl and methotrexate (MTX) alone exhibited inhibitory effects not only on proliferation and efflux pump of cultured cancer cells but also pathogenic biofilm formation. Phytopolyphenols (P) and MTX potentiated these inhibitory effects of Cl. In addition, novel regimens containing Cl, memantine (Mem) or thioridazine (TRZ) further enhanced not only efficacy and selectivity of anticancer effects but also inhibition on efflux pump and pathogenic biofilm formation of four chemotherapeutic agents (MTX, cisplatin, 5-fluorouracil and doxorubicin) respectively.

Conclusion

In this study, novel regimens of phytopolyphenols (P), targeting drugs (T; Cl, Mem or TRZ) and metal ions (M; ZnSO4) so called PTM regimens exerted not only by themselves but also markedly potentiated efficacy and selectivity of anticancer effects of four chemotherapeutic agents. Because of their potent inhibitions on efflux pump and pathogenic biofilm formation, these combinatorial novel regimens were expected to be able to overcome the problems of multidrug resistant cancers and merit for further clinical studies.

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来源期刊
Journal of Dental Sciences
Journal of Dental Sciences 医学-牙科与口腔外科
CiteScore
5.10
自引率
14.30%
发文量
348
审稿时长
6 days
期刊介绍: he Journal of Dental Sciences (JDS), published quarterly, is the official and open access publication of the Association for Dental Sciences of the Republic of China (ADS-ROC). The precedent journal of the JDS is the Chinese Dental Journal (CDJ) which had already been covered by MEDLINE in 1988. As the CDJ continued to prove its importance in the region, the ADS-ROC decided to move to the international community by publishing an English journal. Hence, the birth of the JDS in 2006. The JDS is indexed in the SCI Expanded since 2008. It is also indexed in Scopus, and EMCare, ScienceDirect, SIIC Data Bases. The topics covered by the JDS include all fields of basic and clinical dentistry. Some manuscripts focusing on the study of certain endemic diseases such as dental caries and periodontal diseases in particular regions of any country as well as oral pre-cancers, oral cancers, and oral submucous fibrosis related to betel nut chewing habit are also considered for publication. Besides, the JDS also publishes articles about the efficacy of a new treatment modality on oral verrucous hyperplasia or early oral squamous cell carcinoma.
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