Cervical Cancer Remains a Serious Global Health Challenge
Cervical cancer is the second most common gynecologic cancer worldwide and remains a major cause of cancer-related death in women. In 2018 alone, an estimated 18.1 million new cancer cases were reported globally. While early detection methods such as cervical cytology screening have improved outcomes, the survival rate for advanced or recurrent cervical cancer is still low. In such cases, only 16.5% of patients survive five years after diagnosis.
This cancer often develops due to infection with high-risk human papillomavirus (HPV). However, several other factors also play a role in its progression. These include deregulation of enzymes like caspases, overexpression of vascular endothelial growth factor (VEGF), immune system failure, and increased levels of proteins that prevent normal cell death.
Current treatment options include surgery, radiotherapy, and chemotherapy—either alone or in combination. Although these therapies are often effective for early-stage disease, their impact is limited in more advanced cases. This highlights the need for more targeted and efficient treatment options.
A Closer Look at Andrographolide
Andrographolide (AND) is a compound derived from the plant Andrographis paniculata. It has drawn increasing interest due to its wide-ranging biological activities. These include anti-tumor, anti-inflammatory, anti-viral, and immunomodulatory properties. In recent years, AND has shown potential in halting the growth, migration, and spread of various cancer cell types. However, its exact role in treating cervical cancer has remained unclear.
Testing a New Model for a Complex Disease
To better evaluate the effects of AND on cervical cancer, researchers from Jiangxi Provincial Cancer Hospital and Case Western Reserve University used a chorioallantoic membrane patient-derived xenograft (CAM-PDX) model. This approach combines two existing tumor modeling methods—the PDX and CAM systems—to create a platform that is both biologically relevant and cost-effective.
The CAM-PDX model uses fertilized chicken eggs to grow patient-derived tumor tissue. It offers a faster, less expensive alternative to mouse models while still capturing the complexity and heterogeneity of human tumors. As lead researcher Wanwan Zou and colleagues report, “the CAM-PDX model provides a suitable tumor microenvironment that accurately simulates the growth characteristics of human tumors.”
Building the CAM-PDX Model
The study began with tumor tissue from a 55-year-old woman diagnosed with stage IIA squamous cell carcinoma (SCC) of the cervix. After establishing a PDX model in mice, the tumor was successfully transferred to the CAM system. The tumors grown in the CAM-PDX model showed similar features to those in the original patient sample, including protein markers such as p40 and CK5/6.
Key Finding: Andrographolide Reduces Tumor Growth and Blood Vessel Formation
The researchers tested AND both alone and in combination with cisplatin (CDDP), a commonly used chemotherapy drug. They found that a 20 mg/kg dose of AND significantly reduced tumor size and blood vessel formation. The combination of AND and CDDP showed an even greater effect than either treatment alone.
Visual inspection of the tumors showed that untreated samples were surrounded by large, branching blood vessels. In contrast, tumors treated with AND appeared pale and had far fewer vessels. Histological analysis confirmed that the treated tumors were poorly differentiated, with disrupted structures and signs of tissue damage.
Understanding the Mechanism
To understand how AND exerts its effects, the team examined several key proteins involved in cell survival and angiogenesis. They found that AND reduced the levels of Ki67, a marker of cell proliferation, as well as B-cell lymphoma 2 (BCL-2), a protein that prevents cell death. It also lowered expression of ERG, a transcription factor linked to the formation of new blood vessels.
These results suggest that AND slows tumor growth by both preventing new blood vessels from forming and triggering cancer cells to die.
Potential Applications and Next Steps
The study shows that the CAM-PDX model is not only effective for growing cervical cancer tumors but also useful for evaluating new treatments. This could help researchers quickly screen other drug candidates, especially those derived from traditional herbal medicine.
By demonstrating the anti-tumor effects of AND in this model, the study offers a promising direction for future treatment strategies. It also opens the door to testing combination therapies that use AND alongside existing chemotherapy drugs.
The authors note that further studies are needed to explore how AND may influence the tumor immune environment. This includes understanding whether AND can support immune-based treatments like checkpoint inhibitors.
Conclusion
This research highlights a low-cost, biologically relevant model for evaluating cervical cancer treatments. It also identifies andrographolide as a promising agent for reducing tumor growth and blood vessel formation in cervical SCC. These findings lay the groundwork for future studies and may help bring more effective therapies to patients with advanced disease.
The translation of the preceding English text in Chinese:
宫颈癌仍是全球严重的公共卫生问题
宫颈癌是全球第二常见的妇科恶性肿瘤，仍是导致女性癌症相关死亡的主要原因之一。仅在2018年，全球就报告了约1810万例新发癌症病例。尽管宫颈细胞学筛查等早期发现方法改善了治疗效果，但对于晚期或复发性宫颈癌，患者的生存率依然很低。在此类病例中，仅有16.5%的患者能在确诊后生存五年。
宫颈癌常因感染高危型人乳头瘤病毒（HPV）而发展。然而，其他多种因素也参与其进展过程，包括半胱天冬酶等酶的异常调控、血管内皮生长因子（VEGF）的过度表达、免疫系统功能失调，以及阻止细胞正常凋亡的蛋白质水平升高等。
目前的治疗手段包括手术、放疗和化疗，三者可单独使用，也可联合应用。尽管这些治疗对早期疾病通常有效，但对晚期病例的疗效有限，凸显出研发更具靶向性和高效性的治疗方案的迫切性。
穿心莲内酯的研究引发关注
穿心莲内酯（Andrographolide，简称AND）是一种来源于穿心莲（Andrographis paniculata）的天然化合物，近年来因其广泛的生物活性而受到关注。这些活性包括抗肿瘤、抗炎、抗病毒和免疫调节等。已有研究显示，AND可抑制多种癌细胞的生长、迁移和扩散。然而，其在治疗宫颈癌中的具体作用机制仍不清楚。
复杂疾病的新模型测试
为了更好地评估AND对宫颈癌的作用，江西省肿瘤医院与美国凯斯西储大学的研究人员共同采用了绒毛尿囊膜患者来源异种移植（CAM-PDX）模型。该方法结合了两种现有的肿瘤建模手段——PDX模型和CAM模型，创建出一种兼具生物相关性和成本效益的研究平台。
CAM-PDX模型利用受精鸡卵培养患者来源的肿瘤组织，作为小鼠模型的更快速、低成本替代方案，同时保留了人类肿瘤的复杂性和异质性。正如首席研究员邹婉婉博士所指出的：“CAM-PDX模型提供了一个适宜的肿瘤微环境，能够准确模拟人类肿瘤的生长特征。”
构建CAM-PDX模型的过程
该研究使用了一名55岁女性宫颈鳞状细胞癌（SCC）IIA期患者的肿瘤组织。研究人员首先在小鼠中建立了PDX模型，然后将肿瘤移植至CAM系统中。在CAM-PDX模型中生长的肿瘤组织与原始样本在蛋白表达上高度相似，包括p40与CK5/6等标志物。
关键发现：穿心莲内酯可抑制肿瘤生长及血管生成
研究人员单独使用AND以及与常用化疗药顺铂（CDDP）联用进行测试。结果表明，20 mg/kg剂量的AND能显著减少肿瘤体积及新生血管形成。而AND与CDDP联合使用的效果优于单药治疗。
肉眼观察显示，未治疗的肿瘤样本被大量分支状血管包围，而经AND处理的肿瘤则颜色变淡，血管数量明显减少。组织学分析进一步确认，处理后的肿瘤分化差，结构紊乱，并出现组织损伤迹象。
作用机制初探
为探明AND的作用机制，研究团队检测了多种与细胞生存及血管生成相关的关键蛋白。结果发现，AND可降低细胞增殖标志物Ki67的水平，并抑制抗凋亡蛋白BCL-2的表达。同时，它还能下调血管生成相关转录因子ERG的表达。
这些结果提示，AND通过抑制血管新生和诱导癌细胞死亡，从而减缓肿瘤生长。
潜在应用与未来方向
研究显示，CAM-PDX模型不仅适用于培养宫颈癌组织，也为新药物的评估提供了可行平台。这种模型有助于快速筛选，尤其是源自传统草药的候选化合物。
本研究通过该模型展示了AND的抗肿瘤效果，为未来治疗策略提供了有前景的方向，也为开发联合疗法（如AND与标准化疗联用）提供了可能。
研究作者指出，未来的研究还需探讨AND对肿瘤免疫微环境的影响，特别是其是否能增强免疫检查点抑制剂等免疫疗法的效果。
结论
本研究强调了一种低成本、具生物学相关性的宫颈癌治疗评估模型，并识别出穿心莲内酯在宫颈鳞癌中具有抑瘤和抗血管生成的潜力。这些发现为未来研究奠定了基础，或将推动更有效疗法的临床应用。
Reference:
Wanwan Zou, Jun Lou, Yun Yi, Yiming Cui, Xiaoyan Chu
Andrographolide suppresses cervical cancer progression by targeting angiogenesis and inducing apoptosis in a CAM-PDX model.
Biomol Biomed [Internet]. 2025 Feb. 11 [cited 2025 May 13];
Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/11432
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