Ramadan W S, Sait K H, Anfinan N M, Sait H
Clin Exp Obstet Gynecol. 2016;43(3):358-64.
Cisplatin is an important chemotherapeutic agent that is widely used in treatment of several malignancies, but its side effects on normal tissues and organs limit its use. The aim of this study was to evaluate the effect of aqueous extract of sweet fennel alone and in combination with cisplatin on human cervical cancer adenocarcinoma cell line (HeLa cells) searching for an effective, inexpensive therapy with minimal side effects.
HeLa cell line was used to study the cytotoxic effect of different concentrations of the aqueous extract of sweet fennel alone and in combination with 50 μg/ml cisplatin. Quantitative measure of drug interaction was quantified by the combination index. Gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) were used to analyze the sweet fennel decoction. MTT assay was used to examine cell viability percentage. Electron microscopy was applied to study the ultrastructure of the cells.
The phenyl propanoids (23%) and phenols (12%) constituted the highest percentage of the aqueous extract. Increasing the concentration of sweet fennel from 50 μg/ml to 80 μg/ml, decreased the percentage of the cell viability of HeLa cells from 86.74% to 78.28%, respectively. Further decrease to 11.31% was demonstrated when 50 μg/ml of fennel was combined with 50 μg/ml cisplatin (additive effect). In addition to the signs of apoptosis observed in HeLa cells at 50 μg/ml of fennel, disruption of both nuclear and cytoplasmic membranes and presence of autophagolysosomes were noticed at a dose of 80 μg/ml. Combination of 50 μg/ml of cisplatin with 60, 70, and 80 μg/ml of sweet fennel revealed no significant difference in comparison to cisplatin alone. The combination with 50 μg/ml of sweet fennel revealed marked vacuolization of the cytoplasm, fragmentation of the nucleus, and complete disruption of nuclear membrane. CONCLUSIOn: Combination of cisplatin and the 50 μg/ml of the fennel could enhance cervical cancer growth inhibition. This combination could be effective in lowering the dose of single or repeated cumulative courses of cisplatin and hence decreases its hazardous side effects. In vivo studies and the evaluation of different combination doses of cisplatin and sweet fennel are recommended.
顺铂是一种重要的化疗药物，广泛用于多种恶性肿瘤的治疗，但其对正常组织和器官的副作用限制了其应用。本研究旨在评估甜茴香水提取物单独及与顺铂联合应用对人宫颈腺癌癌细胞系（HeLa细胞）的影响，以寻找一种有效、廉价且副作用最小的治疗方法。
使用HeLa细胞系研究不同浓度甜茴香水提取物单独及与50μg/ml顺铂联合应用的细胞毒性作用。通过联合指数对药物相互作用进行定量测定。采用气相色谱-质谱联用（GC-MS）和高效液相色谱（HPLC）分析甜茴香煎剂。采用MTT法检测细胞活力百分比。应用电子显微镜研究细胞超微结构。
苯丙烷类化合物（23%）和酚类（12%）在水提取物中所占比例最高。将甜茴香浓度从50μg/ml提高到80μg/ml，HeLa细胞的活力百分比分别从86.74%降至78.28%。当50μg/ml茴香与50μg/ml顺铂联合应用时，细胞活力进一步降至11.31%（相加作用）。除了在50μg/ml茴香作用下HeLa细胞出现凋亡迹象外，在80μg/ml剂量下还观察到核膜和细胞质膜的破坏以及自噬溶酶体的存在。50μg/ml顺铂与60、70和80μg/ml甜茴香联合应用与单独使用顺铂相比无显著差异。与50μg/ml甜茴香联合应用时，细胞质出现明显空泡化、细胞核碎片化以及核膜完全破坏。
顺铂与50μg/ml茴香联合应用可增强对宫颈癌生长的抑制作用。这种联合应用可能有效降低顺铂单次或重复累积疗程的剂量，从而减少其有害副作用。建议进行体内研究以及评估顺铂与甜茴香不同联合剂量。
