Simultaneous targeting of CD44 and EpCAM with a bispecific aptamer effectively inhibits intraperitoneal ovarian cancer growth

Abstract

CD44 and EpCAM play crucial roles in intraperitoneal ovarian cancer development. In this study, we developed an RNA-based bispecific CD44-EpCAM aptamer that is capable of blocking CD44 and EpCAM simultaneously by fusing single CD44 and EpCAM aptamers with a double stranded RNA adaptor. With the aid of a panel of ovarian cancer cell lines, we found that bispecific CD44-EpCAM aptamer was much more effective than either single CD44 or EpCAM aptamer in the ability to inhibit cell growth and to induce apoptosis. When these aptamers were tested in intraperitoneal ovarian cancer xenograft model, bispecific CD44-EpCAM aptamer suppressed intraperitoneal tumor outgrowth much more significantly than single CD44 and EpCAM aptamer either alone or in combination. The enhanced efficacy of bispecific CD44-EpCAM aptamer is most likely to be attributed to its increased circulation time over the single aptamers. Moreover, we showed that bispecific CD44-EpCAM aptamer exhibited no toxicity to the host and was unable to trigger innate immunogenicity. Our study suggests that bispecific CD44-EpCAM aptamer may represent a promising therapeutic agent against advanced ovarian cancer.

Aptamers for Targeted Delivery: Current Challenges and Future Opportunities

“…Similarly, other works also demonstrated lack of hepatic and renal toxicity in vivo for aptamer-mediated tumor suppression [45,61].…”

“…The only side effect DOI: http://dx.doi.org /10.5772/intechopen.84217 reported arose almost exclusively due to the injection procedure instead of the drug itself [43]. Similarly, other works have also described aptamers as non-toxic therapeutic agents [44,45].…”

Dioscin improves postmenopausal osteoporosis through inducing bone formation and inhibiting apoptosis in ovariectomized rats

“…After 60 days of treatment, histological slices from the right femurs of rats were prepared for ALP and BMP IHC staining, as previously described (14). The slices were analyzed using a microscope Image-Pro Plus 6.0, and positive cells were identified as the cells with brown staining.…”

Dissimilar tumor cell populations in ascitic fluid of ovarian cancer patients

“…Во-первых, нормальные клетки имеют низкий уровень ýкспрессии CD44 и плохую адгезию к гиалуроновой кислоте. Во-вторых, гиалуроновая кислота является одним из основных компонентов внеклеточного матрикса опухоли, который помимо связывания с ЦОК поддерживает целостность клеток [3].…”